chr11-62692522-A-G

Position:

• chr11-62692522-A-G

Variant summary

Our verdict is Benign. Variant got -20 ACMG points: 0P and 20B. BP4_Strong BP6_Very_Strong BA1

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
• Clinical Significance: Benign criteria provided, multiple submitters, no conflicts B:7
• Conservation: PhyloP100: 0.240

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]

HNRNPUL2-BSCL2 (HGNC:):

ACMG classification

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/exons	MANE	UniProt
BSCL2	NM_001122955.4	c.766-49T>C		intron_variant		ENST00000360796.10
HNRNPUL2-BSCL2	NR_037946.1	n.3286-49T>C		intron_variant, non_coding_transcript_variant

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
BSCL2	ENST00000360796.10	c.766-49T>C		intron_variant		1	NM_001122955.4	A2

Frequencies

GnomAD3 genomes AF: 0.753 AC: 114452 AN: 151960 Hom.: 43300 Cov.: 31

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

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.: 35 AF XY: 0.764 AC XY: 553977 AN XY: 725170

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.: 31 AF XY: 0.759 AC XY: 56390 AN XY: 74326

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

Submissions by phenotype

not provided Benign:2

Benign, criteria provided, single submitter	clinical testing	GeneDx	Jun 14, 2018	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. -
Benign, criteria provided, single submitter	not provided	Breakthrough Genomics, Breakthrough Genomics	-	- -

not specified Benign:1

Benign, criteria provided, single submitter

clinical testing

PreventionGenetics, part of Exact Sciences

-

- -

Severe neurodegenerative syndrome with lipodystrophy Benign:1

Benign, criteria provided, single submitter

clinical testing

Genome-Nilou Lab

Jul 14, 2021

- -

Hereditary spastic paraplegia 17 Benign:1

Benign, criteria provided, single submitter

clinical testing

Genome-Nilou Lab

Jul 14, 2021

- -

Neuronopathy, distal hereditary motor, type 5C Benign:1

Benign, criteria provided, single submitter

clinical testing

Genome-Nilou Lab

Jul 14, 2021

- -

Congenital generalized lipodystrophy type 2 Benign:1

Benign, criteria provided, single submitter

clinical testing

Genome-Nilou Lab

Jul 14, 2021

- -

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

Other links and lift over

dbSNP: rs2850597; hg19: chr11-62459994;