rs72929434

Variant names:

• chr11-62702457-C-A
• rs72929434
• NM_001122955.4:c.486+11G>T

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.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:13
• Conservation: PhyloP100: 0.711
• Publications: 7 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=-0.55).
• BP6: Variant 11-62702457-C-A is Benign according to our data. Variant chr11-62702457-C-A is described in ClinVar as Benign. ClinVar VariationId is 257497.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars.
• BA1: GnomAd4 highest subpopulation (NFE) allele frequency at 95% confidence interval = 0.219 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.486+11G>T		intron	N/A	NP_001116427.1	Q96G97-4
	BSCL2	NM_001386027.1		c.486+11G>T		intron	N/A	NP_001372956.1	J3KQ12
	BSCL2	NM_001386028.1		c.486+11G>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.486+11G>T		intron	N/A	ENSP00000354032.5	Q96G97-4
	BSCL2	ENST00000405837.5	TSL:1	c.486+11G>T		intron	N/A	ENSP00000385332.1	J3KQ12
	BSCL2	ENST00000407022.7	TSL:1	c.294+11G>T		intron	N/A	ENSP00000384080.3	Q96G97-2

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

GnomAD2 exomes AF: 0.175 AC: 43944 AN: 250708 AF XY: 0.180

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 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

African (AFR) AF: 0.108 AC: 3600 AN: 33256

American (AMR) AF: 0.136 AC: 6044 AN: 44552

Ashkenazi Jewish (ASJ) AF: 0.159 AC: 4138 AN: 26004

East Asian (EAS) AF: 0.102 AC: 4016 AN: 39542

South Asian (SAS) AF: 0.171 AC: 14670 AN: 86002

European-Finnish (FIN) AF: 0.138 AC: 7310 AN: 53126

Middle Eastern (MID) AF: 0.173 AC: 992 AN: 5746

European-Non Finnish (NFE) AF: 0.229 AC: 252815 AN: 1103404

Other (OTH) AF: 0.188 AC: 11246 AN: 59916

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

African (AFR) AF: 0.111 AC: 4604 AN: 41496

American (AMR) AF: 0.139 AC: 2129 AN: 15284

Ashkenazi Jewish (ASJ) AF: 0.161 AC: 558 AN: 3472

East Asian (EAS) AF: 0.0908 AC: 470 AN: 5174

South Asian (SAS) AF: 0.173 AC: 835 AN: 4822

European-Finnish (FIN) AF: 0.126 AC: 1332 AN: 10580

Middle Eastern (MID) AF: 0.184 AC: 54 AN: 294

European-Non Finnish (NFE) AF: 0.222 AC: 15059 AN: 67982

Other (OTH) AF: 0.175 AC: 370 AN: 2112

Alfa AF: 0.188 Hom.: 1024

Bravo AF: 0.165

Asia WGS AF: 0.127 AC: 443 AN: 3478

ClinVar

ClinVar submissions

Significance: Benign

Revision: criteria provided, multiple submitters, no conflicts

Pathogenic	VUS	Benign	Condition
-	-	4	not specified (4)
-	-	2	Congenital generalized lipodystrophy type 2 (2)
-	-	2	not provided (2)
-	-	1	Charcot-Marie-Tooth disease type 2 (1)
-	-	1	Hereditary spastic paraplegia 17 (1)
-	-	1	Neuronopathy, distal hereditary motor, type 5A (1)
-	-	1	Neuronopathy, distal hereditary motor, type 5C (1)
-	-	1	Severe neurodegenerative syndrome with lipodystrophy (1)

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.55
CADD	Benign	8.7
DANN	Benign	0.88
PhyloP100		0.71
Mutation Taster		=100/0	polymorphism (auto)

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

MaxEntScan Visualizer can be used to analyze the impact of this mutation on the neighboring sequence.

Other links and lift over

dbSNP: rs72929434;

hg19: chr11-62469929;

COSMIC: COSV54015955;

COSMIC: COSV54015955;