Variant 2-226795828-C-T details in Genebe, Genetics Data Aggregator

Variant summary

Our verdict is Benign. Variant got -13 ACMG points: 0P and 13B. BP4_StrongBP6BA1

The ENST00000305123.6(IRS1):c.2911G>A(p.Gly971Arg) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0618 in 1,613,026 control chromosomes in the GnomAD database, including 3,374 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 (no stars).

Frequency

Genomes: 𝑓 0.060 ( 278 hom., cov: 33)

Exomes 𝑓: 0.062 ( 3096 hom. )

Consequence

IRS1
ENST00000305123.6 missense

Scores

Clinical Significance

Benign no assertion criteria provided B:1

Conservation

PhyloP100: 0.972

Variant links:

Genes affected

IRS1 (HGNC:6125): (insulin receptor substrate 1) This gene encodes a protein which is phosphorylated by insulin receptor tyrosine kinase. Mutations in this gene are associated with type II diabetes and susceptibility to insulin resistance. [provided by RefSeq, Nov 2009]

IRS1 links:

Genome browser will be placed here

ACMG classification

Classification made for transcript

Verdict is Benign. Variant got -13 ACMG points.

BP4

Computational evidence support a benign effect (MetaRNN=0.0019664168).

BP6

Variant 2-226795828-C-T is Benign according to our data. Variant chr2-226795828-C-T is described in ClinVar as [Benign]. Clinvar id is 29761.Status of the report is no_assertion_criteria_provided, 0 stars.

BA1

GnomAd4 highest subpopulation (NFE) allele frequency at 95% confidence interval = 0.0651 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein
IRS1	NM_005544.3 linkuse as main transcript	c.2911G>A	p.Gly971Arg	missense_variant	1/2	ENST00000305123.6	NP_005535.1
IRS1	XM_047444223.1 linkuse as main transcript	c.2911G>A	p.Gly971Arg	missense_variant	1/2		XP_047300179.1
IRS1	XM_047444224.1 linkuse as main transcript	c.2911G>A	p.Gly971Arg	missense_variant	1/2		XP_047300180.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
IRS1	ENST00000305123.6 linkuse as main transcript	c.2911G>A	p.Gly971Arg	missense_variant	1/2	1	NM_005544.3	ENSP00000304895	P1

Frequencies

GnomAD3 genomes

AF:

0.0600

AC:

9127

AN:

152192

Hom.:

279

Cov.:

show subpopulations

Gnomad AFR

AF:

0.0625

Gnomad AMI

AF:

0.0471

Gnomad AMR

AF:

0.0503

Gnomad ASJ

AF:

0.0435

Gnomad EAS

AF:

0.0202

Gnomad SAS

AF:

0.0425

Gnomad FIN

AF:

0.0504

Gnomad MID

AF:

0.0728

Gnomad NFE

AF:

0.0668

Gnomad OTH

AF:

0.0774

GnomAD3 exomes

AF:

0.0520

AC:

13009

AN:

250112

Hom.:

386

AF XY:

0.0517

AC XY:

7011

AN XY:

135558

show subpopulations

Gnomad AFR exome

AF:

0.0628

Gnomad AMR exome

AF:

0.0387

Gnomad ASJ exome

AF:

0.0439

Gnomad EAS exome

AF:

0.0139

Gnomad SAS exome

AF:

0.0371

Gnomad FIN exome

AF:

0.0530

Gnomad NFE exome

AF:

0.0651

Gnomad OTH exome

AF:

0.0566

GnomAD4 exome

AF:

0.0620

AC:

90552

AN:

1460716

Hom.:

3096

Cov.:

AF XY:

0.0618

AC XY:

44921

AN XY:

726620

show subpopulations

Gnomad4 AFR exome

AF:

0.0626

Gnomad4 AMR exome

AF:

0.0406

Gnomad4 ASJ exome

AF:

0.0400

Gnomad4 EAS exome

AF:

0.0204

Gnomad4 SAS exome

AF:

0.0387

Gnomad4 FIN exome

AF:

0.0507

Gnomad4 NFE exome

AF:

0.0675

Gnomad4 OTH exome

AF:

0.0570

GnomAD4 genome

AF:

0.0599

AC:

9120

AN:

152310

Hom.:

278

Cov.:

AF XY:

0.0588

AC XY:

4377

AN XY:

74484

show subpopulations

Gnomad4 AFR

AF:

0.0624

Gnomad4 AMR

AF:

0.0502

Gnomad4 ASJ

AF:

0.0435

Gnomad4 EAS

AF:

0.0201

Gnomad4 SAS

AF:

0.0421

Gnomad4 FIN

AF:

0.0504

Gnomad4 NFE

AF:

0.0667

Gnomad4 OTH

AF:

0.0766

Alfa

AF:

0.0626

Hom.:

413

Bravo

AF:

0.0599

TwinsUK

AF:

0.0666

AC:

247

ALSPAC

AF:

0.0638

AC:

246

ESP6500AA

AF:

0.0579

AC:

255

ESP6500EA

AF:

0.0658

AC:

566

ExAC

AF:

0.0525

AC:

6376

Asia WGS

AF:

0.0300

AC:

106

AN:

3478

EpiCase

AF:

0.0702

EpiControl

AF:

0.0718

ClinVar

Significance: Benign

Submissions summary: Benign:1

Revision: no assertion criteria provided

LINK: link

Submissions by phenotype

Insulin resistance, susceptibility to

Benign:1

Benign, no assertion criteria provided

literature only

OMIM

Jul 01, 2004

- -

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

AlphaMissense

Benign

0.13

BayesDel_addAF

Benign

-0.34

BayesDel_noAF

Benign

-0.22

CADD

Benign

DANN

Uncertain

1.0

DEOGEN2

Uncertain

0.45

Eigen

Benign

-0.22

Eigen_PC

Benign

-0.12

FATHMM_MKL

Benign

0.20

LIST_S2

Benign

0.80

MetaRNN

Benign

0.0020

MetaSVM

Benign

-1.0

MutationAssessor

Benign

0.69

MutationTaster

Benign

1.0

PrimateAI

Uncertain

0.50

PROVEAN

Benign

-0.25

REVEL

Benign

0.19

Sift

Benign

0.11

Sift4G

Benign

0.17

Polyphen

0.71

Vest4

0.28

MutPred

0.089

Gain of MoRF binding (P = 0.0115);

MPC

1.0

ClinPred

0.030

GERP RS

5.4

Varity_R

0.12

gMVP

0.44

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

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