rs3763853

Variant names:

• chr11-62705572-C-T
• rs3763853
• NM_001122955.4:c.133G>A

Your query was ambiguous. Multiple possible variants found:

• chr11-62705572-C-T
• chr11-62705572-C-G

Variant summary

Our verdict is Benign. The variant received -20 ACMG points: 0P and 20B. BP4_Strong BP6_Very_Strong BS1 BS2

The NM_001122955.4(BSCL2):​c.133G>A​(p.Gly45Ser) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.000678 in 1,584,782 control chromosomes in the GnomAD database, including 15 homozygotes. In-silico tool predicts a benign outcome for this variant. 11/19 in silico tools predict a benign outcome for this variant. Variant has been reported in ClinVar as Likely benign (★★).

• Frequency:
  • Genomes: 𝑓 0.00034 (0 hom., cov: 32)
  • Exomes 𝑓: 0.00071 (15 hom.)
• Consequence: BSCL2 NM_001122955.4 missense
• Clinical Significance: Benign/Likely benign criteria provided, multiple submitters, no conflicts B:7
• Conservation: PhyloP100: 1.17
• Publications: 4 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 (MetaRNN=0.0064359903).
• BP6: Variant 11-62705572-C-T is Benign according to our data. Variant chr11-62705572-C-T is described in ClinVar as Benign/Likely_benign. ClinVar VariationId is 305183.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars.
• BS1: Variant frequency is greater than expected in population eas. GnomAd4 allele frequency = 0.000341 (52/152296) while in subpopulation EAS AF = 0.00869 (45/5178). AF 95% confidence interval is 0.00667. There are 0 homozygotes in GnomAd4. There are 27 alleles in the male GnomAd4 subpopulation. Median coverage is 32. This position passed quality control check.
• BS2: High Homozygotes in GnomAdExome4 at 15 AD,AR gene

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.133G>A	p.Gly45Ser	missense	Exon 2 of 11	NP_001116427.1	Q96G97-4
	BSCL2	NM_001386027.1		c.133G>A	p.Gly45Ser	missense	Exon 3 of 12	NP_001372956.1	J3KQ12
	BSCL2	NM_001386028.1		c.133G>A	p.Gly45Ser	missense	Exon 3 of 12	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.133G>A	p.Gly45Ser	missense	Exon 2 of 11	ENSP00000354032.5	Q96G97-4
	BSCL2	ENST00000405837.5	TSL:1	c.133G>A	p.Gly45Ser	missense	Exon 3 of 12	ENSP00000385332.1	J3KQ12
	BSCL2	ENST00000407022.7	TSL:1	c.-60G>A		5_prime_UTR	Exon 2 of 11	ENSP00000384080.3	Q96G97-2

Frequencies

GnomAD3 genomes AF: 0.000342 AC: 52 AN: 152178 Hom.: 0 Cov.: 32

Gnomad AFR AF: 0.00

Gnomad AMI AF: 0.00

Gnomad AMR AF: 0.00

Gnomad ASJ AF: 0.00

Gnomad EAS AF: 0.00867

Gnomad SAS AF: 0.00

Gnomad FIN AF: 0.000283

Gnomad MID AF: 0.00

Gnomad NFE AF: 0.0000441

Gnomad OTH AF: 0.000479

GnomAD2 exomes AF: 0.000550 AC: 118 AN: 214402 AF XY: 0.000475

Gnomad AFR exome AF: 0.00

Gnomad AMR exome AF: 0.00

Gnomad ASJ exome AF: 0.00

Gnomad EAS exome AF: 0.00664

Gnomad FIN exome AF: 0.000154

Gnomad NFE exome AF: 0.0000529

Gnomad OTH exome AF: 0.000187

GnomAD4 exome AF: 0.000713 AC: 1022 AN: 1432486 Hom.: 15 Cov.: 31 AF XY: 0.000747 AC XY: 529 AN XY: 708316

African (AFR) AF: 0.00 AC: 0 AN: 33104

American (AMR) AF: 0.00 AC: 0 AN: 40640

Ashkenazi Jewish (ASJ) AF: 0.00 AC: 0 AN: 24962

East Asian (EAS) AF: 0.0247 AC: 965 AN: 39008

South Asian (SAS) AF: 0.0000359 AC: 3 AN: 83570

European-Finnish (FIN) AF: 0.000192 AC: 10 AN: 52200

Middle Eastern (MID) AF: 0.00 AC: 0 AN: 5676

European-Non Finnish (NFE) AF: 0.0000265 AC: 29 AN: 1094098

Other (OTH) AF: 0.000253 AC: 15 AN: 59228

GnomAD4 genome AF: 0.000341 AC: 52 AN: 152296 Hom.: 0 Cov.: 32 AF XY: 0.000363 AC XY: 27 AN XY: 74466

African (AFR) AF: 0.00 AC: 0 AN: 41568

American (AMR) AF: 0.00 AC: 0 AN: 15304

Ashkenazi Jewish (ASJ) AF: 0.00 AC: 0 AN: 3470

East Asian (EAS) AF: 0.00869 AC: 45 AN: 5178

South Asian (SAS) AF: 0.00 AC: 0 AN: 4826

European-Finnish (FIN) AF: 0.000283 AC: 3 AN: 10616

Middle Eastern (MID) AF: 0.00 AC: 0 AN: 294

European-Non Finnish (NFE) AF: 0.0000441 AC: 3 AN: 68020

Other (OTH) AF: 0.000474 AC: 1 AN: 2108

Alfa AF: 0.000544 Hom.: 8

Bravo AF: 0.000125

ExAC AF: 0.000595 AC: 72

Asia WGS AF: 0.00491 AC: 17 AN: 3478

ClinVar

ClinVar submissions

Significance: Benign/Likely benign

Revision: criteria provided, multiple submitters, no conflicts

Pathogenic	VUS	Benign	Condition
-	-	3	not provided (3)
-	-	1	Charcot-Marie-Tooth disease type 2 (1)
-	-	1	Congenital generalized lipodystrophy type 2 (1)
-	-	1	Congenital generalized lipodystrophy type 2;C2931276:Hereditary spastic paraplegia 17;C4014700:Severe neurodegenerative syndrome with lipodystrophy;C5436838:Neuronopathy, distal hereditary motor, type 5C (1)
-	-	1	Neuronopathy, distal hereditary motor, type 5A (1)

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
AlphaMissense	Benign	0.090
BayesDel_addAF	Benign	-0.24	T
BayesDel_noAF	Benign	-0.11
CADD	Benign	23
DANN	Uncertain	1.0
DEOGEN2	Benign	0.036	T
Eigen	Benign	0.15
Eigen_PC	Benign	0.19
FATHMM_MKL	Benign	0.75	D
LIST_S2	Benign	0.84	T
MetaRNN	Benign	0.0064	T
MetaSVM	Uncertain	0.43	D
PhyloP100		1.2
PrimateAI	Benign	0.37	T
PROVEAN	Benign	-0.51	N
REVEL	Uncertain	0.43
Sift	Uncertain	0.013	D
Sift4G	Benign	0.21	T
Vest4		0.063
MVP		0.85
ClinPred		0.047	T
GERP RS		5.1
RBP_binding_hub_radar		0.0
RBP_regulation_power_radar		1.7
gMVP		0.11
Mutation Taster		=78/22	polymorphism

Splicing

Name	Calibrated prediction	Score	Prediction
SpliceAI score (max)		0.030		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: rs3763853; hg19: chr11-62473044;