rs72929419

Positions:

• chr11-62691191-A-C

Variant summary

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

The ENST00000360796.10(BSCL2):​c.1006-50T>G variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0253 in 1,613,856 control chromosomes in the GnomAD database, including 689 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Likely benign (★★).

• Frequency:
  • Genomes: 𝑓 0.021 (41 hom., cov: 32)
  • Exomes 𝑓: 0.026 (648 hom.)
• Consequence: BSCL2 ENST00000360796.10 intron
• Clinical Significance: Benign/Likely benign criteria provided, multiple submitters, no conflicts B:3
• Conservation: PhyloP100: -0.344

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=-0.88).
• BP6: Variant 11-62691191-A-C is Benign according to our data. Variant chr11-62691191-A-C is described in ClinVar as [Likely_benign]. Clinvar id is 257496.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars. Variant chr11-62691191-A-C is described in Lovd as [Benign].
• BA1: GnomAdExome4 highest subpopulation (MID) allele frequency at 95% confidence interval = 0.0816 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
BSCL2	NM_001122955.4	c.1006-50T>G		intron_variant		ENST00000360796.10	NP_001116427.1
HNRNPUL2-BSCL2	NR_037946.1	n.3526-50T>G		intron_variant, non_coding_transcript_variant

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
BSCL2	ENST00000360796.10	c.1006-50T>G		intron_variant		1	NM_001122955.4	ENSP00000354032	A2

Frequencies

GnomAD3 genomes AF: 0.0210 AC: 3201 AN: 152136 Hom.: 39 Cov.: 32

Gnomad AFR AF: 0.00504

Gnomad AMI AF: 0.0439

Gnomad AMR AF: 0.0226

Gnomad ASJ AF: 0.0951

Gnomad EAS AF: 0.00

Gnomad SAS AF: 0.00601

Gnomad FIN AF: 0.0300

Gnomad MID AF: 0.0732

Gnomad NFE AF: 0.0272

Gnomad OTH AF: 0.0272

GnomAD3 exomes AF: 0.0232 AC: 5841 AN: 251318 Hom.: 110 AF XY: 0.0237 AC XY: 3223 AN XY: 135864

Gnomad AFR exome AF: 0.00425

Gnomad AMR exome AF: 0.0149

Gnomad ASJ exome AF: 0.0930

Gnomad EAS exome AF: 0.000218

Gnomad SAS exome AF: 0.00800

Gnomad FIN exome AF: 0.0308

Gnomad NFE exome AF: 0.0283

Gnomad OTH exome AF: 0.0313

GnomAD4 exome AF: 0.0258 AC: 37679 AN: 1461600 Hom.: 648 Cov.: 32 AF XY: 0.0258 AC XY: 18759 AN XY: 727128

Gnomad4 AFR exome AF: 0.00460

Gnomad4 AMR exome AF: 0.0160

Gnomad4 ASJ exome AF: 0.0936

Gnomad4 EAS exome AF: 0.000126

Gnomad4 SAS exome AF: 0.00853

Gnomad4 FIN exome AF: 0.0317

Gnomad4 NFE exome AF: 0.0267

Gnomad4 OTH exome AF: 0.0295

GnomAD4 genome AF: 0.0210 AC: 3199 AN: 152256 Hom.: 41 Cov.: 32 AF XY: 0.0206 AC XY: 1537 AN XY: 74448

Gnomad4 AFR AF: 0.00503

Gnomad4 AMR AF: 0.0226

Gnomad4 ASJ AF: 0.0951

Gnomad4 EAS AF: 0.00

Gnomad4 SAS AF: 0.00601

Gnomad4 FIN AF: 0.0300

Gnomad4 NFE AF: 0.0272

Gnomad4 OTH AF: 0.0279

Alfa AF: 0.0314 Hom.: 16

Bravo AF: 0.0206

Asia WGS AF: 0.00346 AC: 12 AN: 3478

ClinVar

Significance: Benign/Likely benign

Submissions summary: Benign:3

Revision: criteria provided, multiple submitters, no conflicts

Submissions by phenotype

not provided Benign:2

Likely benign, criteria provided, single submitter	not provided	Breakthrough Genomics, Breakthrough Genomics	-	- -
Likely benign, criteria provided, single submitter	clinical testing	GeneDx	Jun 26, 2018	- -

not specified Benign:1

Benign, criteria provided, single submitter

clinical testing

PreventionGenetics, part of Exact Sciences

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Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.88
CADD	Benign	1.3
DANN	Benign	0.65
RBP_binding_hub_radar		0.0
RBP_regulation_power_radar		1.1

Splicing

Name	Calibrated prediction	Score	Prediction
SpliceAI score (max)		0.0		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: rs72929419; hg19: chr11-62458663;