rs72929419

Variant names:

• chr11-62691191-A-C
• rs72929419
• NM_001122955.4:c.1006-50T>G

Your query was ambiguous. Multiple possible variants found:

• chr11-62691191-A-C
• chr11-62691191-A-G

Variant summary

Our verdict is Benign. The variant received -20 ACMG points: 0P and 20B. BP4_Strong BP6_Very_Strong BA1

The NM_001122955.4(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 NM_001122955.4 intron
• Clinical Significance: Benign/Likely benign criteria provided, multiple submitters, no conflicts B:3
• Conservation: PhyloP100: -0.344
• Publications: 5 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 -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 Benign/Likely_benign. ClinVar VariationId is 257496.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars.
• BA1: GnomAdExome4 highest subpopulation (MID) allele frequency at 95% confidence interval = 0.0816 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.1006-50T>G		intron	N/A	NP_001116427.1	Q96G97-4
	BSCL2	NM_001386027.1		c.1006-50T>G		intron	N/A	NP_001372956.1	J3KQ12
	BSCL2	NM_001386028.1		c.1006-50T>G		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.1006-50T>G		intron	N/A	ENSP00000354032.5	Q96G97-4
	BSCL2	ENST00000405837.5	TSL:1	c.1006-50T>G		intron	N/A	ENSP00000385332.1	J3KQ12
	BSCL2	ENST00000407022.7	TSL:1	c.814-50T>G		intron	N/A	ENSP00000384080.3	Q96G97-2

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

GnomAD2 exomes AF: 0.0232 AC: 5841 AN: 251318 AF XY: 0.0237

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 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

African (AFR) AF: 0.00460 AC: 154 AN: 33474

American (AMR) AF: 0.0160 AC: 714 AN: 44716

Ashkenazi Jewish (ASJ) AF: 0.0936 AC: 2445 AN: 26132

East Asian (EAS) AF: 0.000126 AC: 5 AN: 39700

South Asian (SAS) AF: 0.00853 AC: 736 AN: 86244

European-Finnish (FIN) AF: 0.0317 AC: 1691 AN: 53420

Middle Eastern (MID) AF: 0.0879 AC: 507 AN: 5768

European-Non Finnish (NFE) AF: 0.0267 AC: 29644 AN: 1111760

Other (OTH) AF: 0.0295 AC: 1783 AN: 60386

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

African (AFR) AF: 0.00503 AC: 209 AN: 41560

American (AMR) AF: 0.0226 AC: 345 AN: 15280

Ashkenazi Jewish (ASJ) AF: 0.0951 AC: 330 AN: 3470

East Asian (EAS) AF: 0.00 AC: 0 AN: 5174

South Asian (SAS) AF: 0.00601 AC: 29 AN: 4822

European-Finnish (FIN) AF: 0.0300 AC: 319 AN: 10618

Middle Eastern (MID) AF: 0.0646 AC: 19 AN: 294

European-Non Finnish (NFE) AF: 0.0272 AC: 1849 AN: 68012

Other (OTH) AF: 0.0279 AC: 59 AN: 2114

Alfa AF: 0.0235 Hom.: 82

Bravo AF: 0.0206

Asia WGS AF: 0.00346 AC: 12 AN: 3478

ClinVar

ClinVar submissions

Significance: Benign/Likely benign

Revision: criteria provided, multiple submitters, no conflicts

Pathogenic	VUS	Benign	Condition
-	-	2	not provided (2)
-	-	1	not specified (1)

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.88
CADD	Benign	1.3
DANN	Benign	0.65
PhyloP100		-0.34
RBP_binding_hub_radar		0.0
RBP_regulation_power_radar		1.1
Mutation Taster		=100/0	polymorphism (auto)

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

Other links and lift over

dbSNP: rs72929419; hg19: chr11-62458663;