11-62692522-A-G

Variant names:

Variant summary

Our verdict is Benign. Variant got -20 ACMG points: 0P and 20B. BP4_StrongBP6_Very_StrongBA1

The NM_001122955.4(BSCL2):c.766-49T>C variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.761 in 1,609,882 control chromosomes in the GnomAD database, including 467,733 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★★).

Frequency

Genomes: 𝑓 0.75 ( 43324 hom., cov: 31)

Exomes 𝑓: 0.76 ( 424409 hom. )

Consequence

BSCL2
NM_001122955.4 intron

Scores

Clinical Significance

Benign criteria provided, multiple submitters, no conflicts B:7

Conservation

PhyloP100: 0.240

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 made for transcript

Verdict is Benign. Variant got -20 ACMG points.

BP4

Computational evidence support a benign effect (BayesDel_noAF=-0.91).

BP6

Variant 11-62692522-A-G is Benign according to our data. Variant chr11-62692522-A-G is described in ClinVar as [Benign]. Clinvar id is 257500.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars. Variant chr11-62692522-A-G is described in Lovd as [Benign].

BA1

GnomAd4 highest subpopulation (AMR) allele frequency at 95% confidence interval = 0.818 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
BSCL2	NM_001122955.4 link	c.766-49T>C		intron_variant	Intron 5 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.766-49T>C		intron_variant	Intron 5 of 10	1	NM_001122955.4	ENSP00000354032.5		Q96G97-4
HNRNPUL2-BSCL2	ENST00000403734.2 link	n.*817-49T>C		intron_variant	Intron 18 of 23	2		ENSP00000456010.1		H3BQZ7

Frequencies

GnomAD3 genomes

AF:

0.753

AC:

114452

AN:

151960

Hom.:

43300

Cov.:

show subpopulations

Gnomad AFR

AF:

0.675

Gnomad AMI

AF:

0.803

Gnomad AMR

AF:

0.830

Gnomad ASJ

AF:

0.771

Gnomad EAS

AF:

0.772

Gnomad SAS

AF:

0.787

Gnomad FIN

AF:

0.854

Gnomad MID

AF:

0.785

Gnomad NFE

AF:

0.762

Gnomad OTH

AF:

0.754

GnomAD3 exomes

AF:

0.781

AC:

192316

AN:

246176

Hom.:

75279

AF XY:

0.781

AC XY:

104024

AN XY:

133154

show subpopulations

Gnomad AFR exome

AF:

0.672

Gnomad AMR exome

AF:

0.847

Gnomad ASJ exome

AF:

0.772

Gnomad EAS exome

AF:

0.769

Gnomad SAS exome

AF:

0.803

Gnomad FIN exome

AF:

0.848

Gnomad NFE exome

AF:

0.761

Gnomad OTH exome

AF:

0.792

GnomAD4 exome

AF:

0.762

AC:

1111342

AN:

1457804

Hom.:

424409

Cov.:

AF XY:

0.764

AC XY:

553977

AN XY:

725170

show subpopulations

Gnomad4 AFR exome

AF:

0.663

Gnomad4 AMR exome

AF:

0.846

Gnomad4 ASJ exome

AF:

0.772

Gnomad4 EAS exome

AF:

0.747

Gnomad4 SAS exome

AF:

0.800

Gnomad4 FIN exome

AF:

0.844

Gnomad4 NFE exome

AF:

0.755

Gnomad4 OTH exome

AF:

0.772

GnomAD4 genome

AF:

0.753

AC:

114525

AN:

152078

Hom.:

43324

Cov.:

AF XY:

0.759

AC XY:

56390

AN XY:

74326

show subpopulations

Gnomad4 AFR

AF:

0.675

Gnomad4 AMR

AF:

0.830

Gnomad4 ASJ

AF:

0.771

Gnomad4 EAS

AF:

0.772

Gnomad4 SAS

AF:

0.789

Gnomad4 FIN

AF:

0.854

Gnomad4 NFE

AF:

0.762

Gnomad4 OTH

AF:

0.752

Alfa

AF:

0.762

Hom.:

9106

Bravo

AF:

0.747

Asia WGS

AF:

0.786

AC:

2732

AN:

3478

ClinVar

Significance: Benign

Submissions summary: Benign:7

Revision: criteria provided, multiple submitters, no conflicts

LINK: link

Submissions by phenotype

not provided

Benign:2

Jun 14, 2018

GeneDx

Significance: Benign

Review Status: criteria provided, single submitter

Collection Method: clinical testing

This variant is considered likely benign or benign based on one or more of the following criteria: it is a conservative change, it occurs at a poorly conserved position in the protein, it is predicted to be benign by multiple in silico algorithms, and/or has population frequency not consistent with disease. -

Breakthrough Genomics, Breakthrough Genomics

Significance: Benign

Review Status: criteria provided, single submitter

Collection Method: not provided

- -

not specified

Benign:1

PreventionGenetics, part of Exact Sciences

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

- -

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

- -

Congenital generalized lipodystrophy type 2

Benign:1

Jul 14, 2021

Genome-Nilou Lab

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

-0.91

CADD

Benign

4.5

DANN

Benign

0.38

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

LitVar

Below is the list of publications found by LitVar. It may be empty.

Variant summary

Frequency

Consequence

Scores

Clinical Significance

Conservation

ACMG classification

Transcripts

RefSeq

Ensembl

Frequencies

ClinVar

Submissions by phenotype

Computational scores

Splicing

Publications

LitVar

Other links and lift over