rs201493373

Variant names:

Variant summary

Our verdict is Likely benign. The variant received -5 ACMG points: 0P and 5B. BP4_StrongBP6

The NM_001122955.4(BSCL2):c.124C>T(p.Arg42Cys) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.000842 in 1,566,712 control chromosomes in the GnomAD database, including 1 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Conflicting classifications of pathogenicity (no stars).

Frequency

Genomes: 𝑓 0.00055 ( 0 hom., cov: 32)

Exomes 𝑓: 0.00087 ( 1 hom. )

Consequence

BSCL2
NM_001122955.4 missense

Scores

Clinical Significance

Conflicting classifications of pathogenicity criteria provided, conflicting classifications U:1B:6

Conservation

PhyloP100: 2.30

Publications

7 publications found

Variant links:

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]

BSCL2 links:

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]

HNRNPUL2-BSCL2 links:

Genome browser will be placed here

ACMG classification

Classification was made for transcript

Our verdict: Likely_benign. The variant received -5 ACMG points.

BP4

Computational evidence support a benign effect (MetaRNN=0.04375255).

BP6

Variant 11-62705581-G-A is Benign according to our data. Variant chr11-62705581-G-A is described in ClinVar as Conflicting_classifications_of_pathogenicity. ClinVar VariationId is 305185.

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

Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
BSCL2	NM_001122955.4	MANE Select	c.124C>T	p.Arg42Cys	missense	Exon 2 of 11	NP_001116427.1	Q96G97-4
BSCL2	NM_001386027.1		c.124C>T	p.Arg42Cys	missense	Exon 3 of 12	NP_001372956.1	J3KQ12
BSCL2	NM_001386028.1		c.124C>T	p.Arg42Cys	missense	Exon 3 of 12	NP_001372957.1	Q96G97-4

Ensembl Transcripts

Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
BSCL2	ENST00000360796.10	TSL:1 MANE Select	c.124C>T	p.Arg42Cys	missense	Exon 2 of 11	ENSP00000354032.5	Q96G97-4
BSCL2	ENST00000405837.5	TSL:1	c.124C>T	p.Arg42Cys	missense	Exon 3 of 12	ENSP00000385332.1	J3KQ12
BSCL2	ENST00000407022.7	TSL:1	c.-69C>T		5_prime_UTR	Exon 2 of 11	ENSP00000384080.3	Q96G97-2

Frequencies

GnomAD3 genomes

AF:

0.000552

AC:

AN:

152140

Hom.:

Cov.:

show subpopulations

Gnomad AFR

AF:

0.000241

Gnomad AMI

AF:

0.00

Gnomad AMR

AF:

0.000131

Gnomad ASJ

AF:

0.00

Gnomad EAS

AF:

0.00

Gnomad SAS

AF:

0.00

Gnomad FIN

AF:

0.0000942

Gnomad MID

AF:

0.00

Gnomad NFE

AF:

0.00101

Gnomad OTH

AF:

0.000958

GnomAD2 exomes

AF:

0.000599

AC:

114

AN:

190236

AF XY:

0.000566

show subpopulations

Gnomad AFR exome

AF:

0.00

Gnomad AMR exome

AF:

0.000575

Gnomad ASJ exome

AF:

0.00

Gnomad EAS exome

AF:

0.00

Gnomad FIN exome

AF:

0.000166

Gnomad NFE exome

AF:

0.00113

Gnomad OTH exome

AF:

0.000612

GnomAD4 exome

AF:

0.000873

AC:

1235

AN:

1414572

Hom.:

Cov.:

AF XY:

0.000811

AC XY:

566

AN XY:

697544

show subpopulations

African (AFR)

AF:

0.000153

AC:

AN:

32768

American (AMR)

AF:

0.000507

AC:

AN:

37446

Ashkenazi Jewish (ASJ)

AF:

0.00

AC:

AN:

24282

East Asian (EAS)

AF:

0.00

AC:

AN:

38558

South Asian (SAS)

AF:

0.00

AC:

AN:

81518

European-Finnish (FIN)

AF:

0.000332

AC:

AN:

51170

Middle Eastern (MID)

AF:

0.000355

AC:

AN:

5636

European-Non Finnish (NFE)

AF:

0.00107

AC:

1164

AN:

1084720

Other (OTH)

AF:

0.000479

AC:

AN:

58474

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.474

Heterozygous variant carriers

147

221

294

368

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Exome Het

Variant carriers

100

150

200

250

<30

30-35

35-40

40-45

45-50

50-55

55-60

60-65

65-70

70-75

75-80

>80

Age

GnomAD4 genome

AF:

0.000552

AC:

AN:

152140

Hom.:

Cov.:

AF XY:

0.000578

AC XY:

AN XY:

74340

show subpopulations

African (AFR)

AF:

0.000241

AC:

AN:

41428

American (AMR)

AF:

0.000131

AC:

AN:

15276

Ashkenazi Jewish (ASJ)

AF:

0.00

AC:

AN:

3468

East Asian (EAS)

AF:

0.00

AC:

AN:

5194

South Asian (SAS)

AF:

0.00

AC:

AN:

4822

European-Finnish (FIN)

AF:

0.0000942

AC:

AN:

10618

Middle Eastern (MID)

AF:

0.00

AC:

AN:

316

European-Non Finnish (NFE)

AF:

0.00101

AC:

AN:

68018

Other (OTH)

AF:

0.000958

AC:

AN:

2088

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.481

Heterozygous variant carriers

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Genome Het

Variant carriers

<30

30-35

35-40

40-45

45-50

50-55

55-60

60-65

65-70

70-75

75-80

>80

Age

Alfa

AF:

0.000810

Hom.:

Bravo

AF:

0.000559

TwinsUK

AF:

0.00

AC:

ALSPAC

AF:

0.00130

AC:

ESP6500AA

AF:

0.00

AC:

ESP6500EA

AF:

0.000943

AC:

ExAC

AF:

0.000632

AC:

ClinVar

ClinVar submissions

Significance:Conflicting classifications of pathogenicity

Revision:criteria provided, conflicting classifications

View on ClinVar

Pathogenic

VUS

Benign

Condition

not provided (4)

Congenital generalized lipodystrophy type 2 (1)

Neuronopathy, distal hereditary motor, type 5A (1)

not specified (1)

Computational scores

Source: dbNSFP v4.9

Name

Calibrated prediction

Score

Prediction

AlphaMissense

Benign

0.16

BayesDel_addAF

Benign

-0.22

BayesDel_noAF

Benign

-0.12

CADD

Pathogenic

(source)

DANN

Pathogenic

1.0

DEOGEN2

Benign

0.028

Eigen

Uncertain

0.36

Eigen_PC

Uncertain

0.36

FATHMM_MKL

Uncertain

0.79

LIST_S2

Uncertain

0.90

M_CAP

Uncertain

0.19

MetaRNN

Benign

0.044

MetaSVM

Uncertain

0.56

PhyloP100

2.3

PrimateAI

Benign

0.36

PROVEAN

Benign

-0.52

REVEL

Uncertain

0.38

Sift

Pathogenic

0.0

Sift4G

Pathogenic

0.0

Vest4

0.38

MVP

0.88

ClinPred

0.094

GERP RS

5.1

RBP_binding_hub_radar

0.0

RBP_regulation_power_radar

1.7

gMVP

0.13

Mutation Taster

=295/5

polymorphism

(source)

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

Publications

You must be logged in to view publications. This limit was set because tens of millions (!) of queries from AI bots are generated daily.

Variant summary

Frequency

Consequence

Scores

Clinical Significance

Conservation

Publications

ACMG classification

Variant Effect in Transcripts

RefSeq Transcripts

Ensembl Transcripts

Frequencies

Age Distribution

Age Distribution

ClinVar

Computational scores

Splicing

Publications

Other links and lift over