rs79586077

Variant names:

• chr11-62692648-G-A
• rs79586077
• NM_001122955.4:c.765+15C>T

Your query was ambiguous. Multiple possible variants found:

• chr11-62692648-G-A
• chr11-62692648-G-C

Variant summary

Our verdict is Benign. The variant received -16 ACMG points: 0P and 16B. BP6_Very_Strong BA1

The NM_001122955.4(BSCL2):​c.765+15C>T variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00683 in 1,613,842 control chromosomes in the GnomAD database, including 634 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★★).

• Frequency:
  • Genomes: 𝑓 0.037 (340 hom., cov: 32)
  • Exomes 𝑓: 0.0037 (294 hom.)
• Consequence: BSCL2 NM_001122955.4 intron
• Clinical Significance: Benign criteria provided, multiple submitters, no conflicts B:6
• Conservation: PhyloP100: -0.268
• Publications: 2 publications found

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: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]

ACMG classification

Our verdict: Benign. The variant received -16 ACMG points.

• BP6: Variant 11-62692648-G-A is Benign according to our data. Variant chr11-62692648-G-A is described in ClinVar as Benign. ClinVar VariationId is 257499.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars.
• BA1: GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.124 is higher than 0.05.

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_001122955.4. You can select a different transcript below to see updated ACMG assignments.

RefSeq Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	BSCL2	NM_001122955.4	MANE Select	c.765+15C>T		intron	N/A	NP_001116427.1	Q96G97-4
	BSCL2	NM_001386027.1		c.765+15C>T		intron	N/A	NP_001372956.1	J3KQ12
	BSCL2	NM_001386028.1		c.765+15C>T		intron	N/A	NP_001372957.1	Q96G97-4

Ensembl Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	BSCL2	ENST00000360796.10	TSL:1 MANE Select	c.765+15C>T		intron	N/A	ENSP00000354032.5	Q96G97-4
	BSCL2	ENST00000405837.5	TSL:1	c.765+15C>T		intron	N/A	ENSP00000385332.1	J3KQ12
	BSCL2	ENST00000407022.7	TSL:1	c.573+15C>T		intron	N/A	ENSP00000384080.3	Q96G97-2

Frequencies

GnomAD3 genomes AF: 0.0368 AC: 5598 AN: 152086 Hom.: 340 Cov.: 32

Gnomad AFR AF: 0.127

Gnomad AMI AF: 0.00

Gnomad AMR AF: 0.0171

Gnomad ASJ AF: 0.000289

Gnomad EAS AF: 0.00

Gnomad SAS AF: 0.000207

Gnomad FIN AF: 0.00

Gnomad MID AF: 0.00633

Gnomad NFE AF: 0.000647

Gnomad OTH AF: 0.0210

GnomAD2 exomes AF: 0.00974 AC: 2447 AN: 251228 AF XY: 0.00705

Gnomad AFR exome AF: 0.131

Gnomad AMR exome AF: 0.00653

Gnomad ASJ exome AF: 0.00

Gnomad EAS exome AF: 0.00

Gnomad FIN exome AF: 0.00

Gnomad NFE exome AF: 0.000624

Gnomad OTH exome AF: 0.00326

GnomAD4 exome AF: 0.00370 AC: 5412 AN: 1461638 Hom.: 294 Cov.: 34 AF XY: 0.00323 AC XY: 2348 AN XY: 727120

African (AFR) AF: 0.129 AC: 4333 AN: 33480

American (AMR) AF: 0.00675 AC: 302 AN: 44722

Ashkenazi Jewish (ASJ) AF: 0.0000383 AC: 1 AN: 26136

East Asian (EAS) AF: 0.00 AC: 0 AN: 39700

South Asian (SAS) AF: 0.000162 AC: 14 AN: 86252

European-Finnish (FIN) AF: 0.00 AC: 0 AN: 53182

Middle Eastern (MID) AF: 0.00573 AC: 33 AN: 5764

European-Non Finnish (NFE) AF: 0.000258 AC: 287 AN: 1112010

Other (OTH) AF: 0.00732 AC: 442 AN: 60392

GnomAD4 genome AF: 0.0368 AC: 5607 AN: 152204 Hom.: 340 Cov.: 32 AF XY: 0.0351 AC XY: 2614 AN XY: 74418

African (AFR) AF: 0.127 AC: 5254 AN: 41500

American (AMR) AF: 0.0171 AC: 262 AN: 15286

Ashkenazi Jewish (ASJ) AF: 0.000289 AC: 1 AN: 3466

East Asian (EAS) AF: 0.00 AC: 0 AN: 5168

South Asian (SAS) AF: 0.00 AC: 0 AN: 4822

European-Finnish (FIN) AF: 0.00 AC: 0 AN: 10612

Middle Eastern (MID) AF: 0.00680 AC: 2 AN: 294

European-Non Finnish (NFE) AF: 0.000647 AC: 44 AN: 68030

Other (OTH) AF: 0.0208 AC: 44 AN: 2116

Alfa AF: 0.00938 Hom.: 19

Bravo AF: 0.0406

Asia WGS AF: 0.00520 AC: 18 AN: 3478

ClinVar

ClinVar submissions

Significance: Benign

Revision: criteria provided, multiple submitters, no conflicts

Pathogenic	VUS	Benign	Condition
-	-	2	not provided (2)
-	-	1	Charcot-Marie-Tooth disease type 2 (1)
-	-	1	Congenital generalized lipodystrophy type 2 (1)
-	-	1	Neuronopathy, distal hereditary motor, type 5A (1)
-	-	1	not specified (1)

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.61
CADD	Benign	17
DANN	Benign	0.82
PhyloP100		-0.27
PromoterAI		-0.014	Neutral
Mutation Taster		=100/0	polymorphism (auto)

Splicing

Name	Calibrated prediction	Score	Prediction
SpliceAI score (max)		0.36		Details are displayed if max score is > 0.2
DS_DG_spliceai		0.36		Position offset: 6

Find out detailed SpliceAI scores and Pangolin per-transcript scores at spliceailookup.broadinstitute.org

Other links and lift over

dbSNP: rs79586077; hg19: chr11-62460120;