Variant rs1801162 details in Genebe, Genetics Data Aggregator

Variant summary

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

The NM_001379150.1(IRS4):c.100C>T(p.Leu34Phe) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0597 in 1,208,866 control chromosomes in the GnomAD database, including 1,581 homozygotes. There are 23,175 hemizygotes in GnomAD. 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 Lovd as Benign (no stars).

Frequency

Genomes: 𝑓 0.061 ( 180 hom., 1875 hem., cov: 22)

Exomes 𝑓: 0.060 ( 1401 hom. 21300 hem. )

Consequence

IRS4
NM_001379150.1 missense

Scores

Clinical Significance

Not reported in ClinVar

Conservation

PhyloP100: 0.356

Variant links:

Genes affected

IRS4 (HGNC:6128): (insulin receptor substrate 4) IRS4 encodes the insulin receptor substrate 4, a cytoplasmic protein that contains many potential tyrosine and serine/threonine phosphorylation sites. Tyrosine-phosphorylated IRS4 protein has been shown to associate with cytoplasmic signalling molecules that contain SH2 domains. The IRS4 protein is phosphorylated by the insulin receptor tyrosine kinase upon receptor stimulation.. [provided by RefSeq, Jul 2008]

IRS4 links:

IRS4-AS1 (HGNC:):

IRS4-AS1 links:

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ACMG classification

Classification made for transcript

Verdict is Benign. Variant got -13 ACMG points.

BP4

Computational evidence support a benign effect (MetaRNN=0.0014205873).

BP6

Variant X-108736245-G-A is Benign according to our data. Variant chrX-108736245-G-A is described in Lovd as [Benign].

BA1

GnomAd4 highest subpopulation (AMR) allele frequency at 95% confidence interval = 0.0743 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
IRS4	NM_001379150.1 linkuse as main transcript	c.100C>T	p.Leu34Phe	missense_variant	1/2	ENST00000372129.4	NP_001366079.1
IRS4	NM_003604.2 linkuse as main transcript	c.100C>T	p.Leu34Phe	missense_variant	1/1		NP_003595.1	O14654
IRS4	XM_011531061.2 linkuse as main transcript	c.100C>T	p.Leu34Phe	missense_variant	1/3		XP_011529363.1
IRS4	XM_006724713.4 linkuse as main transcript	c.100C>T	p.Leu34Phe	missense_variant	1/2		XP_006724776.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	UniProt
IRS4	ENST00000372129.4 linkuse as main transcript	c.100C>T	p.Leu34Phe	missense_variant	1/2	6	NM_001379150.1	ENSP00000361202.3	A0A804CF45
IRS4	ENST00000564206.2 linkuse as main transcript	c.100C>T	p.Leu34Phe	missense_variant	1/1	6		ENSP00000505547.1	O14654
IRS4-AS1	ENST00000608811.1 linkuse as main transcript	n.235G>A		non_coding_transcript_exon_variant	1/2	4
IRS4-AS1	ENST00000668534.1 linkuse as main transcript	n.155G>A		non_coding_transcript_exon_variant	1/3

Frequencies

GnomAD3 genomes

AF:

0.0608

AC:

6770

AN:

111344

Hom.:

179

Cov.:

AF XY:

0.0555

AC XY:

1864

AN XY:

33568

show subpopulations

Gnomad AFR

AF:

0.0696

Gnomad AMI

AF:

0.0150

Gnomad AMR

AF:

0.0784

Gnomad ASJ

AF:

0.0432

Gnomad EAS

AF:

0.000859

Gnomad SAS

AF:

0.0574

Gnomad FIN

AF:

0.0359

Gnomad MID

AF:

0.0598

Gnomad NFE

AF:

0.0603

Gnomad OTH

AF:

0.0710

GnomAD3 exomes

AF:

0.0557

AC:

10048

AN:

180245

Hom.:

226

AF XY:

0.0530

AC XY:

3524

AN XY:

66531

show subpopulations

Gnomad AFR exome

AF:

0.0727

Gnomad AMR exome

AF:

0.0854

Gnomad ASJ exome

AF:

0.0447

Gnomad EAS exome

AF:

0.000439

Gnomad SAS exome

AF:

0.0594

Gnomad FIN exome

AF:

0.0303

Gnomad NFE exome

AF:

0.0578

Gnomad OTH exome

AF:

0.0530

GnomAD4 exome

AF:

0.0596

AC:

65377

AN:

1097471

Hom.:

1401

Cov.:

AF XY:

0.0586

AC XY:

21300

AN XY:

363243

show subpopulations

Gnomad4 AFR exome

AF:

0.0701

Gnomad4 AMR exome

AF:

0.0826

Gnomad4 ASJ exome

AF:

0.0424

Gnomad4 EAS exome

AF:

0.000199

Gnomad4 SAS exome

AF:

0.0584

Gnomad4 FIN exome

AF:

0.0326

Gnomad4 NFE exome

AF:

0.0623

Gnomad4 OTH exome

AF:

0.0571

GnomAD4 genome

AF:

0.0609

AC:

6784

AN:

111395

Hom.:

180

Cov.:

AF XY:

0.0558

AC XY:

1875

AN XY:

33629

show subpopulations

Gnomad4 AFR

AF:

0.0698

Gnomad4 AMR

AF:

0.0787

Gnomad4 ASJ

AF:

0.0432

Gnomad4 EAS

AF:

0.000861

Gnomad4 SAS

AF:

0.0583

Gnomad4 FIN

AF:

0.0359

Gnomad4 NFE

AF:

0.0602

Gnomad4 OTH

AF:

0.0701

Alfa

AF:

0.0584

Hom.:

2612

Bravo

AF:

0.0637

TwinsUK

AF:

0.0634

AC:

235

ALSPAC

AF:

0.0633

AC:

183

ESP6500AA

AF:

0.0668

AC:

256

ESP6500EA

AF:

0.0583

AC:

392

ExAC

AF:

0.0555

AC:

6736

EpiCase

AF:

0.0609

EpiControl

AF:

0.0601

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

AlphaMissense

Benign

0.11

BayesDel_addAF

Benign

-0.86

BayesDel_noAF

Benign

-0.95

CADD

Benign

DANN

Uncertain

0.98

DEOGEN2

Benign

0.19

FATHMM_MKL

Benign

0.18

LIST_S2

Benign

0.43

MetaRNN

Benign

0.0014

MetaSVM

Benign

-1.0

MutationAssessor

Benign

0.90

PrimateAI

Uncertain

0.74

PROVEAN

Benign

-0.44

REVEL

Benign

0.021

Sift

Benign

0.081

Sift4G

Benign

0.20

Polyphen

0.0020

Vest4

0.037

MPC

0.66

ClinPred

0.0036

GERP RS

0.36

Varity_R

0.090

gMVP

0.26

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

Computational scores

Splicing

Publications

LitVar

Other links and lift over