rs72929434

chr11-62702457-C-A

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.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
• Clinical Significance: Benign criteria provided, multiple submitters, no conflicts B:11
• Conservation: PhyloP100: 0.711

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=-0.55).
• BP6: Variant 11-62702457-C-A is Benign according to our data. Variant chr11-62702457-C-A is described in ClinVar 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 Lovd as [Benign].
• 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/exons	MANE	UniProt
BSCL2	NM_001122955.4	c.486+11G>T		intron_variant		ENST00000360796.10
HNRNPUL2-BSCL2	NR_037946.1	n.3006+11G>T		intron_variant, non_coding_transcript_variant

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
BSCL2	ENST00000360796.10	c.486+11G>T		intron_variant		1	NM_001122955.4	A2

Frequencies

GnomAD3 genomes AF: 0.168 AC: 25591 AN: 152010 Hom.: 2343 Cov.: 31

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

GnomAD3 exomes AF: 0.175 AC: 43944 AN: 250708 Hom.: 4160 AF XY: 0.180 AC XY: 24328 AN XY: 135500

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 SAS exome AF: 0.168

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.: 31 AF XY: 0.209 AC XY: 151016 AN XY: 722588

Gnomad4 AFR exome AF: 0.108

Gnomad4 AMR exome AF: 0.136

Gnomad4 ASJ exome AF: 0.159

Gnomad4 EAS exome AF: 0.102

Gnomad4 SAS exome AF: 0.171

Gnomad4 FIN exome AF: 0.138

Gnomad4 NFE exome AF: 0.229

Gnomad4 OTH exome AF: 0.188

GnomAD4 genome AF: 0.168 AC: 25591 AN: 152128 Hom.: 2343 Cov.: 31 AF XY: 0.164 AC XY: 12192 AN XY: 74376

Gnomad4 AFR AF: 0.111

Gnomad4 AMR AF: 0.139

Gnomad4 ASJ AF: 0.161

Gnomad4 EAS AF: 0.0908

Gnomad4 SAS AF: 0.173

Gnomad4 FIN AF: 0.126

Gnomad4 NFE AF: 0.222

Gnomad4 OTH AF: 0.175

Alfa AF: 0.190 Hom.: 533

Bravo AF: 0.165

Asia WGS AF: 0.127 AC: 443 AN: 3478

ClinVar

Significance: Benign

Submissions summary: Benign:11

Revision: criteria provided, multiple submitters, no conflicts

Submissions by phenotype

not specified Benign:3

Benign, no assertion criteria provided	clinical testing	Clinical Genetics, Academic Medical Center	-	- -
Benign, no assertion criteria provided	clinical testing	Joint Genome Diagnostic Labs from Nijmegen and Maastricht, Radboudumc and MUMC+	-	- -
Benign, criteria provided, single submitter	clinical testing	PreventionGenetics, part of Exact Sciences	-	- -

Congenital generalized lipodystrophy type 2 Benign:2

Benign, criteria provided, single submitter	clinical testing	Genome-Nilou Lab	Jul 14, 2021	- -
Benign, criteria provided, single submitter	clinical testing	Illumina Laboratory Services, Illumina	Jan 13, 2018	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. -

Severe neurodegenerative syndrome with lipodystrophy Benign:1

Benign, criteria provided, single submitter

clinical testing

Genome-Nilou Lab

Jul 14, 2021

- -

Charcot-Marie-Tooth disease type 2 Benign:1

Benign, criteria provided, single submitter

clinical testing

Invitae

Feb 01, 2024

- -

Hereditary spastic paraplegia 17 Benign:1

Benign, criteria provided, single submitter

clinical testing

Genome-Nilou Lab

Jul 14, 2021

- -

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

Benign, criteria provided, single submitter

clinical testing

Illumina Laboratory Services, Illumina

Jan 13, 2018

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. -

not provided Benign:1

Benign, criteria provided, single submitter

clinical testing

GeneDx

Mar 03, 2015

- -

Neuronopathy, distal hereditary motor, type 5C 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	-0.55
Cadd	Benign	8.7
Dann	Benign	0.88

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: rs72929434; hg19: chr11-62469929; COSMIC: COSV54015955; COSMIC: COSV54015955;