rs6856

Variant names:

Your query was ambiguous. Multiple possible variants found:

Variant summary

Our verdict is Benign. The variant received -21 ACMG points: 0P and 21B. BP4_StrongBP6_Very_StrongBP7BA1

The NM_001122955.4(BSCL2):c.1137A>G(p.Glu379Glu) variant causes a synonymous change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.206 in 1,613,344 control chromosomes in the GnomAD database, including 35,885 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★★).

Frequency

Genomes: 𝑓 0.17 ( 2289 hom., cov: 33)

Exomes 𝑓: 0.21 ( 33596 hom. )

Consequence

BSCL2
NM_001122955.4 synonymous

Scores

Clinical Significance

Benign criteria provided, multiple submitters, no conflicts P:1B:13

Conservation

PhyloP100: -0.198

Publications

26 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 -21 ACMG points.

BP4

Computational evidence support a benign effect (MetaRNN=0.0010504425).

BP6

Variant 11-62690803-T-C is Benign according to our data. Variant chr11-62690803-T-C is described in ClinVar as Benign. ClinVar VariationId is 128533.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars.

BP7

Synonymous conserved (PhyloP=-0.198 with no splicing effect.

BA1

GnomAd4 highest subpopulation (NFE) allele frequency at 95% confidence interval = 0.218 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
BSCL2	NM_001122955.4 link	c.1137A>G	p.Glu379Glu	synonymous_variant	Exon 9 of 11	ENST00000360796.10	NP_001116427.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein
BSCL2	ENST00000360796.10 link	c.1137A>G	p.Glu379Glu	synonymous_variant	Exon 9 of 11	1	NM_001122955.4	ENSP00000354032.5
HNRNPUL2-BSCL2	ENST00000403734.2 link	n.*1188A>G		non_coding_transcript_exon_variant	Exon 22 of 24	2		ENSP00000456010.1
HNRNPUL2-BSCL2	ENST00000403734.2 link	n.*1188A>G		3_prime_UTR_variant	Exon 22 of 24	2		ENSP00000456010.1

Frequencies

GnomAD3 genomes

AF:

0.166

AC:

25255

AN:

152094

Hom.:

2289

Cov.:

show subpopulations

Gnomad AFR

AF:

0.103

Gnomad AMI

AF:

0.196

Gnomad AMR

AF:

0.139

Gnomad ASJ

AF:

0.161

Gnomad EAS

AF:

0.0906

Gnomad SAS

AF:

0.172

Gnomad FIN

AF:

0.126

Gnomad MID

AF:

0.177

Gnomad NFE

AF:

0.221

Gnomad OTH

AF:

0.176

GnomAD2 exomes

AF:

0.174

AC:

42637

AN:

245200

AF XY:

0.178

show subpopulations

Gnomad AFR exome

AF:

0.106

Gnomad AMR exome

AF:

0.136

Gnomad ASJ exome

AF:

0.158

Gnomad EAS exome

AF:

0.0832

Gnomad FIN exome

AF:

0.131

Gnomad NFE exome

AF:

0.223

Gnomad OTH exome

AF:

0.171

GnomAD4 exome

AF:

0.210

AC:

307367

AN:

1461132

Hom.:

33596

Cov.:

AF XY:

0.209

AC XY:

152096

AN XY:

726820

show subpopulations

African (AFR)

AF:

0.0996

AC:

3335

AN:

33480

American (AMR)

AF:

0.136

AC:

6072

AN:

44710

Ashkenazi Jewish (ASJ)

AF:

0.160

AC:

4178

AN:

26132

East Asian (EAS)

AF:

0.102

AC:

4047

AN:

39700

South Asian (SAS)

AF:

0.169

AC:

14569

AN:

86244

European-Finnish (FIN)

AF:

0.138

AC:

7287

AN:

52934

Middle Eastern (MID)

AF:

0.174

AC:

1002

AN:

5768

European-Non Finnish (NFE)

AF:

0.230

AC:

255547

AN:

1111794

Other (OTH)

AF:

0.188

AC:

11330

AN:

60370

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.471

Heterozygous variant carriers

15430

30861

46291

61722

77152

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Exome Het

Exome Hom

Variant carriers

8624

17248

25872

34496

43120

<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:

0.166

AC:

25260

AN:

152212

Hom.:

2289

Cov.:

AF XY:

0.162

AC XY:

12026

AN XY:

74430

show subpopulations

African (AFR)

AF:

0.103

AC:

4292

AN:

41542

American (AMR)

AF:

0.139

AC:

2126

AN:

15296

Ashkenazi Jewish (ASJ)

AF:

0.161

AC:

557

AN:

3468

East Asian (EAS)

AF:

0.0904

AC:

467

AN:

5166

South Asian (SAS)

AF:

0.171

AC:

828

AN:

4834

European-Finnish (FIN)

AF:

0.126

AC:

1342

AN:

10618

Middle Eastern (MID)

AF:

0.180

AC:

AN:

294

European-Non Finnish (NFE)

AF:

0.221

AC:

15047

AN:

67974

Other (OTH)

AF:

0.175

AC:

370

AN:

2110

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.495

Heterozygous variant carriers

1082

2164

3247

4329

5411

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Genome Het

Genome Hom

Variant carriers

272

544

816

1088

1360

<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:

0.201

Hom.:

10787

Bravo

AF:

0.163

TwinsUK

AF:

0.237

AC:

878

ALSPAC

AF:

0.228

AC:

877

ESP6500AA

AF:

0.112

AC:

492

ESP6500EA

AF:

0.220

AC:

1891

ExAC

AF:

0.177

AC:

21428

Asia WGS

AF:

0.127

AC:

443

AN:

3478

EpiCase

AF:

0.232

EpiControl

AF:

0.241

ClinVar

Significance: Benign

Submissions summary: Pathogenic:1Benign:13

Revision: criteria provided, multiple submitters, no conflicts

LINK: link

Submissions by phenotype

not specified

Benign:2

PreventionGenetics, part of Exact Sciences

Significance:Benign

Review Status:criteria provided, single submitter

Collection Method:clinical testing

- -

Genetic Services Laboratory, University of Chicago

Significance:Likely benign

Review Status:no assertion criteria provided

Collection Method:clinical testing

Likely benign based on allele frequency in 1000 Genomes Project or ESP global frequency and its presence in a patient with a rare or unrelated disease phenotype. NOT Sanger confirmed. -

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

- -

Isolated systolic hypertension;C4021419:Triangular shaped proximal phalanx of the thumb;C5139433:Neutrophilia in presence of infection

Pathogenic:1

Phenosystems SA

Significance:Pathogenic

Review Status:no assertion criteria provided

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

Benign:1

Dec 12, 2016

Genome Diagnostics Laboratory, The Hospital for Sick Children

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

- -

Lipodystrophy

Benign:1

Apr 17, 2023

Department of Pathology and Laboratory Medicine, Sinai Health System

Significance:Benign

Review Status:criteria provided, single submitter

Collection Method:research

- -

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

AlphaMissense

Benign

0.077

BayesDel_addAF

Benign

-0.27

BayesDel_noAF

Uncertain

-0.020

CADD

Benign

5.6

(source)

DANN

Uncertain

0.98

Eigen

Benign

-0.93

Eigen_PC

Benign

-1.0

FATHMM_MKL

Benign

0.024

LIST_S2

Benign

0.44

MetaRNN

Benign

0.0011

MetaSVM

Benign

-1.1

PhyloP100

-0.20

PROVEAN

Benign

-0.21

REVEL

Benign

0.20

Sift

Benign

0.19

Sift4G

Benign

0.51

Polyphen

0.0

Vest4

0.14

ClinPred

0.0016

GERP RS

-3.9

RBP_binding_hub_radar

0.0

RBP_regulation_power_radar

1.1

Mutation Taster

=100/0

polymorphism (auto)

(source)

Splicing

Name

Calibrated prediction

Score

Prediction

SpliceAI score (max)

0.050

Details are displayed if max score is > 0.2

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

Publications

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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