Variant 10-95315108-T-C details in Genebe, Genetics Data Aggregator

Variant summary

Our verdict is Benign. Variant got -14 ACMG points: 0P and 14B. BP4_StrongBP6_ModerateBA1

The NM_001034954.3(SORBS1):c.3830A>G(p.Lys1277Arg) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00316 in 1,613,856 control chromosomes in the GnomAD database, including 151 homozygotes. In-silico tool predicts a benign outcome for this variant. 13/20 in silico tools predict a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★).

Frequency

Genomes: 𝑓 0.017 ( 86 hom., cov: 32)

Exomes 𝑓: 0.0017 ( 65 hom. )

Consequence

SORBS1
NM_001034954.3 missense

Scores

Clinical Significance

Benign criteria provided, single submitter B:1

Conservation

PhyloP100: 2.80

Variant links:

Genes affected

SORBS1 (HGNC:14565): (sorbin and SH3 domain containing 1) This gene encodes a CBL-associated protein which functions in the signaling and stimulation of insulin. Mutations in this gene may be associated with human disorders of insulin resistance. Alternative splicing results in multiple transcript variants. [provided by RefSeq, Mar 2014]

SORBS1 links:

Genome browser will be placed here

ACMG classification

Classification made for transcript

Verdict is Benign. Variant got -14 ACMG points.

BP4

Computational evidence support a benign effect (MetaRNN=0.00283736).

BP6

Variant 10-95315108-T-C is Benign according to our data. Variant chr10-95315108-T-C is described in ClinVar as [Benign]. Clinvar id is 709983.Status of the report is criteria_provided_single_submitter, 1 stars. Variant chr10-95315108-T-C is described in Lovd as [Benign].

BA1

GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.0577 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
SORBS1	NM_001034954.3 linkuse as main transcript	c.3830A>G	p.Lys1277Arg	missense_variant	33/33	ENST00000371247.7

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
SORBS1	ENST00000371247.7 linkuse as main transcript	c.3830A>G	p.Lys1277Arg	missense_variant	33/33	5	NM_001034954.3	P3	Q9BX66-1

Frequencies

GnomAD3 genomes

AF:

0.0172

AC:

2615

AN:

152198

Hom.:

Cov.:

show subpopulations

Gnomad AFR

AF:

0.0596

Gnomad AMI

AF:

0.00

Gnomad AMR

AF:

0.00720

Gnomad ASJ

AF:

0.00

Gnomad EAS

AF:

0.00

Gnomad SAS

AF:

0.000207

Gnomad FIN

AF:

0.00

Gnomad MID

AF:

0.00

Gnomad NFE

AF:

0.000132

Gnomad OTH

AF:

0.0115

GnomAD3 exomes

AF:

0.00485

AC:

1216

AN:

250916

Hom.:

AF XY:

0.00362

AC XY:

491

AN XY:

135660

show subpopulations

Gnomad AFR exome

AF:

0.0663

Gnomad AMR exome

AF:

0.00324

Gnomad ASJ exome

AF:

0.00

Gnomad EAS exome

AF:

0.00

Gnomad SAS exome

AF:

0.0000654

Gnomad FIN exome

AF:

0.00

Gnomad NFE exome

AF:

0.0000883

Gnomad OTH exome

AF:

0.00245

GnomAD4 exome

AF:

0.00170

AC:

2479

AN:

1461540

Hom.:

Cov.:

AF XY:

0.00147

AC XY:

1072

AN XY:

727104

show subpopulations

Gnomad4 AFR exome

AF:

0.0608

Gnomad4 AMR exome

AF:

0.00387

Gnomad4 ASJ exome

AF:

0.00

Gnomad4 EAS exome

AF:

0.00

Gnomad4 SAS exome

AF:

0.0000812

Gnomad4 FIN exome

AF:

0.00

Gnomad4 NFE exome

AF:

0.0000306

Gnomad4 OTH exome

AF:

0.00356

GnomAD4 genome

AF:

0.0172

AC:

2624

AN:

152316

Hom.:

Cov.:

AF XY:

0.0165

AC XY:

1230

AN XY:

74478

show subpopulations

Gnomad4 AFR

AF:

0.0597

Gnomad4 AMR

AF:

0.00719

Gnomad4 ASJ

AF:

0.00

Gnomad4 EAS

AF:

0.00

Gnomad4 SAS

AF:

0.000207

Gnomad4 FIN

AF:

0.00

Gnomad4 NFE

AF:

0.000132

Gnomad4 OTH

AF:

0.0114

Alfa

AF:

0.00386

Hom.:

Bravo

AF:

0.0206

TwinsUK

AF:

0.000270

AC:

ALSPAC

AF:

0.00

AC:

ESP6500AA

AF:

0.0550

AC:

242

ESP6500EA

AF:

0.000233

AC:

ExAC

AF:

0.00597

AC:

725

Asia WGS

AF:

0.00404

AC:

AN:

3478

EpiCase

AF:

0.000164

EpiControl

AF:

0.000119

ClinVar

Significance: Benign

Submissions summary: Benign:1

Revision: criteria provided, single submitter

LINK: link

Submissions by phenotype

not provided

Benign:1

Benign, criteria provided, single submitter

clinical testing

Invitae

Jul 23, 2018

- -

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

AlphaMissense

Benign

0.043

BayesDel_addAF

Benign

-0.61

BayesDel_noAF

Benign

-0.60

Cadd

Benign

Dann

Benign

0.24

Eigen

Benign

-0.40

Eigen_PC

Benign

-0.18

FATHMM_MKL

Benign

0.21

LIST_S2

Benign

0.55

T;T;T;T;T;T;T;T;T;.;.;T;T;T;T

MetaRNN

Benign

0.0028

T;T;T;T;T;T;T;T;T;T;T;T;T;T;T

MetaSVM

Benign

-1.1

MutationTaster

Benign

0.68

D;D;D;D;D;D;D;D;D;N;N;N;N;N

PrimateAI

Pathogenic

0.83

PROVEAN

Benign

0.16

N;.;N;N;N;N;.;.;.;N;N;N;N;N;N

REVEL

Benign

0.12

Sift

Benign

1.0

T;.;T;T;T;T;.;.;.;T;T;T;T;T;T

Sift4G

Benign

0.80

T;.;T;T;T;T;T;.;.;T;T;T;T;T;T

Polyphen

0.0

B;.;B;B;B;B;.;.;.;B;B;B;B;B;B

Vest4

0.13

MVP

0.54

MPC

0.15

ClinPred

0.0075

GERP RS

5.8

Varity_R

0.026

gMVP

0.23

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

LitVar

Below is the list of publications found by LitVar. It may be empty.

Variant summary

Frequency

Consequence

Scores

Clinical Significance

Conservation

ACMG classification

Transcripts

RefSeq

Ensembl

Frequencies

ClinVar

Submissions by phenotype

Computational scores

Splicing

Publications

LitVar

Other links and lift over