11-62705456-G-A

Variant names:

Variant summary

Our verdict is Benign. The variant received -11 ACMG points: 2P and 13B. PM2BP4_StrongBP6_Very_StrongBP7

The NM_001122955.4(BSCL2):c.249C>T(p.Val83Val) variant causes a synonymous change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00000248 in 1,614,146 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Likely benign (★★).

Frequency

Genomes: 𝑓 0.0000066 ( 0 hom., cov: 32)

Exomes 𝑓: 0.0000021 ( 0 hom. )

Consequence

BSCL2
NM_001122955.4 synonymous

Scores

Clinical Significance

Likely benign criteria provided, multiple submitters, no conflicts B:2

Conservation

PhyloP100: 0.200

Publications

0 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 -11 ACMG points.

PM2

Very rare variant in population databases, with high coverage;

BP4

Computational evidence support a benign effect (BayesDel_noAF=-0.71).

BP6

Variant 11-62705456-G-A is Benign according to our data. Variant chr11-62705456-G-A is described in CliVar as Likely_benign. Clinvar id is 476814.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars. Variant chr11-62705456-G-A is described in CliVar as Likely_benign. Clinvar id is 476814.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars. Variant chr11-62705456-G-A is described in CliVar as Likely_benign. Clinvar id is 476814.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars. Variant chr11-62705456-G-A is described in CliVar as Likely_benign. Clinvar id is 476814.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars. Variant chr11-62705456-G-A is described in CliVar as Likely_benign. Clinvar id is 476814.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars. Variant chr11-62705456-G-A is described in CliVar as Likely_benign. Clinvar id is 476814.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars. Variant chr11-62705456-G-A is described in CliVar as Likely_benign. Clinvar id is 476814.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars. Variant chr11-62705456-G-A is described in CliVar as Likely_benign. Clinvar id is 476814.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars. Variant chr11-62705456-G-A is described in CliVar as Likely_benign. Clinvar id is 476814.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars. Variant chr11-62705456-G-A is described in CliVar as Likely_benign. Clinvar id is 476814.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars. Variant chr11-62705456-G-A is described in CliVar as Likely_benign. Clinvar id is 476814.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars. Variant chr11-62705456-G-A is described in CliVar as Likely_benign. Clinvar id is 476814.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars. Variant chr11-62705456-G-A is described in CliVar as Likely_benign. Clinvar id is 476814.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars. Variant chr11-62705456-G-A is described in CliVar as Likely_benign. Clinvar id is 476814.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars. Variant chr11-62705456-G-A is described in CliVar as Likely_benign. Clinvar id is 476814.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars. Variant chr11-62705456-G-A is described in CliVar as Likely_benign. Clinvar id is 476814.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars. Variant chr11-62705456-G-A is described in CliVar as Likely_benign. Clinvar id is 476814.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars. Variant chr11-62705456-G-A is described in CliVar as Likely_benign. Clinvar id is 476814.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars. Variant chr11-62705456-G-A is described in CliVar as Likely_benign. Clinvar id is 476814.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars. Variant chr11-62705456-G-A is described in CliVar as Likely_benign. Clinvar id is 476814.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars. Variant chr11-62705456-G-A is described in CliVar as Likely_benign. Clinvar id is 476814.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars. Variant chr11-62705456-G-A is described in CliVar as Likely_benign. Clinvar id is 476814.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars. Variant chr11-62705456-G-A is described in CliVar as Likely_benign. Clinvar id is 476814.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars. Variant chr11-62705456-G-A is described in CliVar as Likely_benign. Clinvar id is 476814.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars. Variant chr11-62705456-G-A is described in CliVar as Likely_benign. Clinvar id is 476814.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars. Variant chr11-62705456-G-A is described in CliVar as Likely_benign. Clinvar id is 476814.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars. Variant chr11-62705456-G-A is described in CliVar as Likely_benign. Clinvar id is 476814.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars. Variant chr11-62705456-G-A is described in CliVar as Likely_benign. Clinvar id is 476814.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars. Variant chr11-62705456-G-A is described in CliVar as Likely_benign. Clinvar id is 476814.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars. Variant chr11-62705456-G-A is described in CliVar as Likely_benign. Clinvar id is 476814.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars. Variant chr11-62705456-G-A is described in CliVar as Likely_benign. Clinvar id is 476814.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars. Variant chr11-62705456-G-A is described in CliVar as Likely_benign. Clinvar id is 476814.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars. Variant chr11-62705456-G-A is described in CliVar as Likely_benign. Clinvar id is 476814.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars. Variant chr11-62705456-G-A is described in CliVar as Likely_benign. Clinvar id is 476814.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars. Variant chr11-62705456-G-A is described in CliVar as Likely_benign. Clinvar id is 476814.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars. Variant chr11-62705456-G-A is described in CliVar as Likely_benign. Clinvar id is 476814.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars. Variant chr11-62705456-G-A is described in CliVar as Likely_benign. Clinvar id is 476814.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars. Variant chr11-62705456-G-A is described in CliVar as Likely_benign. Clinvar id is 476814.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars. Variant chr11-62705456-G-A is described in CliVar as Likely_benign. Clinvar id is 476814.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars.

BP7

Synonymous conserved (PhyloP=0.2 with no splicing effect.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
BSCL2	NM_001122955.4 link	c.249C>T	p.Val83Val	synonymous_variant	Exon 2 of 11	ENST00000360796.10	NP_001116427.1	Q96G97-4A0A024R540

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	UniProt
BSCL2	ENST00000360796.10 link	c.249C>T	p.Val83Val	synonymous_variant	Exon 2 of 11	1	NM_001122955.4	ENSP00000354032.5	Q96G97-4
HNRNPUL2-BSCL2	ENST00000403734.2 link	n.*300C>T		non_coding_transcript_exon_variant	Exon 15 of 24	2		ENSP00000456010.1	H3BQZ7
HNRNPUL2-BSCL2	ENST00000403734.2 link	n.*300C>T		3_prime_UTR_variant	Exon 15 of 24	2		ENSP00000456010.1	H3BQZ7

Frequencies

GnomAD3 genomes

AF:

0.00000657

AC:

AN:

152252

Hom.:

Cov.:

show subpopulations

Gnomad AFR

AF:

0.00

Gnomad AMI

AF:

0.00

Gnomad AMR

AF:

0.00

Gnomad ASJ

AF:

0.00

Gnomad EAS

AF:

0.000192

Gnomad SAS

AF:

0.00

Gnomad FIN

AF:

0.00

Gnomad MID

AF:

0.00

Gnomad NFE

AF:

0.00

Gnomad OTH

AF:

0.00

GnomAD2 exomes

AF:

0.0000119

AC:

AN:

251246

AF XY:

0.00000736

show subpopulations

Gnomad AFR exome

AF:

0.00

Gnomad AMR exome

AF:

0.00

Gnomad ASJ exome

AF:

0.00

Gnomad EAS exome

AF:

0.000163

Gnomad FIN exome

AF:

0.00

Gnomad NFE exome

AF:

0.00

Gnomad OTH exome

AF:

0.00

GnomAD4 exome

AF:

0.00000205

AC:

AN:

1461894

Hom.:

Cov.:

AF XY:

0.00000138

AC XY:

AN XY:

727248

show subpopulations

⚠️ The allele balance in gnomAD version 4 Exomes is significantly skewed from the expected value of 0.5.

African (AFR)

AF:

0.00

AC:

AN:

33480

American (AMR)

AF:

0.00

AC:

AN:

44724

Ashkenazi Jewish (ASJ)

AF:

0.00

AC:

AN:

26136

East Asian (EAS)

AF:

0.0000756

AC:

AN:

39700

South Asian (SAS)

AF:

0.00

AC:

AN:

86258

European-Finnish (FIN)

AF:

0.00

AC:

AN:

53420

Middle Eastern (MID)

AF:

0.00

AC:

AN:

5768

European-Non Finnish (NFE)

AF:

0.00

AC:

AN:

1112012

Other (OTH)

AF:

0.00

AC:

AN:

60396

⚠️ The allele balance in gnomAD4 Exomes is highly skewed from 0.5 (p-value = 0.001311), which strongly suggests a high chance of mosaicism in these individuals.

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.392

Heterozygous variant carriers

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Exome Het

Variant carriers

<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:

0.00000657

AC:

AN:

152252

Hom.:

Cov.:

AF XY:

0.0000134

AC XY:

AN XY:

74390

show subpopulations

African (AFR)

AF:

0.00

AC:

AN:

41466

American (AMR)

AF:

0.00

AC:

AN:

15286

Ashkenazi Jewish (ASJ)

AF:

0.00

AC:

AN:

3472

East Asian (EAS)

AF:

0.000192

AC:

AN:

5206

South Asian (SAS)

AF:

0.00

AC:

AN:

4834

European-Finnish (FIN)

AF:

0.00

AC:

AN:

10630

Middle Eastern (MID)

AF:

0.00

AC:

AN:

316

European-Non Finnish (NFE)

AF:

0.00

AC:

AN:

68042

Other (OTH)

AF:

0.00

AC:

AN:

2088

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.575

Heterozygous variant carriers

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Genome Het

Variant carriers

<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:

0.00

Hom.:

Bravo

AF:

0.00000756

ClinVar

Significance: Likely benign

Submissions summary: Benign:2

Revision: criteria provided, multiple submitters, no conflicts

LINK: link

Submissions by phenotype

Inborn genetic diseases

Benign:1

Jul 11, 2019

Ambry Genetics

Significance:Likely benign

Review Status:criteria provided, single submitter

Collection Method:clinical testing

This alteration is classified as likely benign based on a combination of the following: seen in unaffected individuals, population frequency, intact protein function, lack of segregation with disease, co-occurrence, RNA analysis, in silico models, amino acid conservation, lack of disease association in case-control studies, and/or the mechanism of disease or impacted region is inconsistent with a known cause of pathogenicity. -

Charcot-Marie-Tooth disease type 2

Benign:1

Aug 15, 2022

Labcorp Genetics (formerly Invitae), Labcorp

Significance:Likely 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

-0.71

CADD

Benign

9.6

(source)

DANN

Benign

0.82

PhyloP100

0.20

Splicing

Name

Calibrated prediction

Score

Prediction

SpliceAI score (max)

0.060

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