rs72929434

Variant names:

Variant summary

Our verdict is Benign. The variant received -20 ACMG points: 0P and 20B. BP4_StrongBP6_Very_StrongBA1

The NM_001122955.4(BSCL2):c.486+11G>T variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.206 in 1,603,676 control chromosomes in the GnomAD database, including 35,706 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★★).

Frequency

Genomes: 𝑓 0.17 ( 2343 hom., cov: 31)

Exomes 𝑓: 0.21 ( 33363 hom. )

Consequence

BSCL2
NM_001122955.4 intron

Scores

Clinical Significance

Benign criteria provided, multiple submitters, no conflicts B:12

Conservation

PhyloP100: 0.711

Publications

7 publications found

Variant links:

Genes affected

BSCL2 (HGNC:15832): (BSCL2 lipid droplet biogenesis associated, seipin) This gene encodes the multi-pass transmembrane protein protein seipin. This protein localizes to the endoplasmic reticulum and may be important for lipid droplet morphology. Mutations in this gene have been associated with congenital generalized lipodystrophy type 2 or Berardinelli-Seip syndrome, a rare autosomal recessive disease characterized by a near absence of adipose tissue and severe insulin resistance. Alternatively spliced transcript variants encoding different isoforms have been found for this gene. Naturally occurring read-through transcription occurs between this locus and the neighboring locus HNRNPUL2 (heterogeneous nuclear ribonucleoprotein U-like 2).[provided by RefSeq, Mar 2011]

BSCL2 links:

HNRNPUL2-BSCL2 (HGNC:49189): (HNRNPUL2-BSCL2 readthrough (NMD candidate)) This locus represents naturally occurring read-through transcription between the neighboring HNRNPUL2 (heterogeneous nuclear ribonucleoprotein U-like 2) and BSCL2 (Berardinelli-Seip congenital lipodystrophy 2 (seipin)) genes on chromosome 11. The read-through transcript is a candidate for nonsense-mediated mRNA decay (NMD), and is unlikely to produce a protein product. [provided by RefSeq, Mar 2011]

HNRNPUL2-BSCL2 links:

Genome browser will be placed here

ACMG classification

Classification was made for transcript

Our verdict: Benign. The variant received -20 ACMG points.

BP4

Computational evidence support a benign effect (BayesDel_noAF=-0.55).

BP6

Variant 11-62702457-C-A is Benign according to our data. Variant chr11-62702457-C-A is described in CliVar as Benign. Clinvar id is 257497.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars. Variant chr11-62702457-C-A is described in CliVar as Benign. Clinvar id is 257497.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars. Variant chr11-62702457-C-A is described in CliVar as Benign. Clinvar id is 257497.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars. Variant chr11-62702457-C-A is described in CliVar as Benign. Clinvar id is 257497.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars. Variant chr11-62702457-C-A is described in CliVar as Benign. Clinvar id is 257497.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars. Variant chr11-62702457-C-A is described in CliVar as Benign. Clinvar id is 257497.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars. Variant chr11-62702457-C-A is described in CliVar as Benign. Clinvar id is 257497.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars. Variant chr11-62702457-C-A is described in CliVar as Benign. Clinvar id is 257497.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars. Variant chr11-62702457-C-A is described in CliVar as Benign. Clinvar id is 257497.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars. Variant chr11-62702457-C-A is described in CliVar as Benign. Clinvar id is 257497.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars. Variant chr11-62702457-C-A is described in CliVar as Benign. Clinvar id is 257497.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars. Variant chr11-62702457-C-A is described in CliVar as Benign. Clinvar id is 257497.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars. Variant chr11-62702457-C-A is described in CliVar as Benign. Clinvar id is 257497.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars. Variant chr11-62702457-C-A is described in CliVar as Benign. Clinvar id is 257497.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars. Variant chr11-62702457-C-A is described in CliVar as Benign. Clinvar id is 257497.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars. Variant chr11-62702457-C-A is described in CliVar as Benign. Clinvar id is 257497.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars. Variant chr11-62702457-C-A is described in CliVar as Benign. Clinvar id is 257497.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars. Variant chr11-62702457-C-A is described in CliVar as Benign. Clinvar id is 257497.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars. Variant chr11-62702457-C-A is described in CliVar as Benign. Clinvar id is 257497.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars. Variant chr11-62702457-C-A is described in CliVar as Benign. Clinvar id is 257497.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars. Variant chr11-62702457-C-A is described in CliVar as Benign. Clinvar id is 257497.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars. Variant chr11-62702457-C-A is described in CliVar as Benign. Clinvar id is 257497.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars. Variant chr11-62702457-C-A is described in CliVar as Benign. Clinvar id is 257497.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars. Variant chr11-62702457-C-A is described in CliVar as Benign. Clinvar id is 257497.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars. Variant chr11-62702457-C-A is described in CliVar as Benign. Clinvar id is 257497.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars. Variant chr11-62702457-C-A is described in CliVar as Benign. Clinvar id is 257497.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars. Variant chr11-62702457-C-A is described in CliVar as Benign. Clinvar id is 257497.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars. Variant chr11-62702457-C-A is described in CliVar as Benign. Clinvar id is 257497.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars. Variant chr11-62702457-C-A is described in CliVar as Benign. Clinvar id is 257497.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars. Variant chr11-62702457-C-A is described in CliVar as Benign. Clinvar id is 257497.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars. Variant chr11-62702457-C-A is described in CliVar as Benign. Clinvar id is 257497.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars. Variant chr11-62702457-C-A is described in CliVar as Benign. Clinvar id is 257497.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars. Variant chr11-62702457-C-A is described in CliVar as Benign. Clinvar id is 257497.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars. Variant chr11-62702457-C-A is described in CliVar as Benign. Clinvar id is 257497.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars. Variant chr11-62702457-C-A is described in CliVar as Benign. Clinvar id is 257497.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars. Variant chr11-62702457-C-A is described in CliVar as Benign. Clinvar id is 257497.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars. Variant chr11-62702457-C-A is described in CliVar as Benign. Clinvar id is 257497.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars.

BA1

GnomAd4 highest subpopulation (NFE) allele frequency at 95% confidence interval = 0.219 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
BSCL2	NM_001122955.4 link	c.486+11G>T		intron_variant	Intron 3 of 10	ENST00000360796.10	NP_001116427.1	Q96G97-4A0A024R540

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
BSCL2	ENST00000360796.10 link	c.486+11G>T		intron_variant	Intron 3 of 10	1	NM_001122955.4	ENSP00000354032.5		Q96G97-4
HNRNPUL2-BSCL2	ENST00000403734.2 link	n.*537+11G>T		intron_variant	Intron 16 of 23	2		ENSP00000456010.1		H3BQZ7

Frequencies

GnomAD3 genomes

AF:

0.168

AC:

25591

AN:

152010

Hom.:

2343

Cov.:

show subpopulations

Gnomad AFR

AF:

0.111

Gnomad AMI

AF:

0.197

Gnomad AMR

AF:

0.139

Gnomad ASJ

AF:

0.161

Gnomad EAS

AF:

0.0910

Gnomad SAS

AF:

0.174

Gnomad FIN

AF:

0.126

Gnomad MID

AF:

0.180

Gnomad NFE

AF:

0.222

Gnomad OTH

AF:

0.176

GnomAD2 exomes

AF:

0.175

AC:

43944

AN:

250708

AF XY:

0.180

show subpopulations

Gnomad AFR exome

AF:

0.112

Gnomad AMR exome

AF:

0.136

Gnomad ASJ exome

AF:

0.157

Gnomad EAS exome

AF:

0.0835

Gnomad FIN exome

AF:

0.131

Gnomad NFE exome

AF:

0.223

Gnomad OTH exome

AF:

0.171

GnomAD4 exome

AF:

0.210

AC:

304831

AN:

1451548

Hom.:

33363

Cov.:

AF XY:

0.209

AC XY:

151016

AN XY:

722588

show subpopulations

African (AFR)

AF:

0.108

AC:

3600

AN:

33256

American (AMR)

AF:

0.136

AC:

6044

AN:

44552

Ashkenazi Jewish (ASJ)

AF:

0.159

AC:

4138

AN:

26004

East Asian (EAS)

AF:

0.102

AC:

4016

AN:

39542

South Asian (SAS)

AF:

0.171

AC:

14670

AN:

86002

European-Finnish (FIN)

AF:

0.138

AC:

7310

AN:

53126

Middle Eastern (MID)

AF:

0.173

AC:

992

AN:

5746

European-Non Finnish (NFE)

AF:

0.229

AC:

252815

AN:

1103404

Other (OTH)

AF:

0.188

AC:

11246

AN:

59916

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.467

Heterozygous variant carriers

11431

22862

34292

45723

57154

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Exome Het

Exome Hom

Variant carriers

8528

17056

25584

34112

42640

<30

30-35

35-40

40-45

45-50

50-55

55-60

60-65

65-70

70-75

75-80

>80

Age

GnomAD4 genome

AF:

0.168

AC:

25591

AN:

152128

Hom.:

2343

Cov.:

AF XY:

0.164

AC XY:

12192

AN XY:

74376

show subpopulations

African (AFR)

AF:

0.111

AC:

4604

AN:

41496

American (AMR)

AF:

0.139

AC:

2129

AN:

15284

Ashkenazi Jewish (ASJ)

AF:

0.161

AC:

558

AN:

3472

East Asian (EAS)

AF:

0.0908

AC:

470

AN:

5174

South Asian (SAS)

AF:

0.173

AC:

835

AN:

4822

European-Finnish (FIN)

AF:

0.126

AC:

1332

AN:

10580

Middle Eastern (MID)

AF:

0.184

AC:

AN:

294

European-Non Finnish (NFE)

AF:

0.222

AC:

15059

AN:

67982

Other (OTH)

AF:

0.175

AC:

370

AN:

2112

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.501

Heterozygous variant carriers

1062

2124

3185

4247

5309

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Genome Het

Genome Hom

Variant carriers

274

548

822

1096

1370

<30

30-35

35-40

40-45

45-50

50-55

55-60

60-65

65-70

70-75

75-80

>80

Age

Alfa

AF:

0.188

Hom.:

1024

Bravo

AF:

0.165

Asia WGS

AF:

0.127

AC:

443

AN:

3478

ClinVar

Significance: Benign

Submissions summary: Benign:12

Revision: criteria provided, multiple submitters, no conflicts

LINK: link

Submissions by phenotype

not specified

Benign:3

PreventionGenetics, part of Exact Sciences

Significance:Benign

Review Status:criteria provided, single submitter

Collection Method:clinical testing

- -

Clinical Genetics, Academic Medical Center

Significance:Benign

Review Status:no assertion criteria provided

Collection Method:clinical testing

- -

Joint Genome Diagnostic Labs from Nijmegen and Maastricht, Radboudumc and MUMC+

Significance:Benign

Review Status:no assertion criteria provided

Collection Method:clinical testing

- -

not provided

Benign:2

Mar 03, 2015

GeneDx

Significance:Benign

Review Status:criteria provided, single submitter

Collection Method:clinical testing

- -

Breakthrough Genomics, Breakthrough Genomics

Significance:Benign

Review Status:criteria provided, single submitter

Collection Method:not provided

- -

Congenital generalized lipodystrophy type 2

Benign:2

Jan 13, 2018

Illumina Laboratory Services, Illumina

Significance:Benign

Review Status:criteria provided, single submitter

Collection Method:clinical testing

This variant was observed in the ICSL laboratory as part of a predisposition screen in an ostensibly healthy population. It had not been previously curated by ICSL or reported in the Human Gene Mutation Database (HGMD: prior to June 1st, 2018), and was therefore a candidate for classification through an automated scoring system. Utilizing variant allele frequency, disease prevalence and penetrance estimates, and inheritance mode, an automated score was calculated to assess if this variant is too frequent to cause the disease. Based on the score and internal cut-off values, a variant classified as benign is not then subjected to further curation. The score for this variant resulted in a classification of benign for this disease. -

Jul 14, 2021

Genome-Nilou Lab

Significance:Benign

Review Status:criteria provided, single submitter

Collection Method:clinical testing

- -

Severe neurodegenerative syndrome with lipodystrophy

Benign:1

Jul 14, 2021

Genome-Nilou Lab

Significance:Benign

Review Status:criteria provided, single submitter

Collection Method:clinical testing

- -

Charcot-Marie-Tooth disease type 2

Benign:1

Feb 03, 2025

Labcorp Genetics (formerly Invitae), Labcorp

Significance:Benign

Review Status:criteria provided, single submitter

Collection Method:clinical testing

- -

Hereditary spastic paraplegia 17

Benign:1

Jul 14, 2021

Genome-Nilou Lab

Significance:Benign

Review Status:criteria provided, single submitter

Collection Method:clinical testing

- -

Neuronopathy, distal hereditary motor, type 5C

Benign:1

Jul 14, 2021

Genome-Nilou Lab

Significance:Benign

Review Status:criteria provided, single submitter

Collection Method:clinical testing

- -

Neuronopathy, distal hereditary motor, type 5A

Benign:1

Jan 13, 2018

Illumina Laboratory Services, Illumina

Significance:Benign

Review Status:criteria provided, single submitter

Collection Method:clinical testing

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

BayesDel_noAF

Benign

-0.55

CADD

Benign

8.7

(source)

DANN

Benign

0.88

PhyloP100

0.71

Mutation Taster

=100/0

polymorphism (auto)

(source)

Splicing

Name

Calibrated prediction

Score

Prediction

SpliceAI score (max)

0.010

Details are displayed if max score is > 0.2

Find out detailed SpliceAI scores and Pangolin per-transcript scores at spliceailookup.broadinstitute.org

Publications

You must be logged in to view publications. This limit was set because tens of millions (!) of queries from AI bots are generated daily.

Variant summary

Frequency

Consequence

Scores

Clinical Significance

Conservation

Publications

ACMG classification

Transcripts

RefSeq

Ensembl

Frequencies

Age Distribution

Age Distribution

ClinVar

Submissions by phenotype

Computational scores

Splicing

Publications

Other links and lift over