Variant rs80131334 details in Genebe, Genetics Data Aggregator

Variant summary

Our verdict is Benign. Variant got -14 ACMG points: 0P and 14B. BP4_StrongBP6BP7BA1

The NM_001379150.1(IRS4):c.1233A>T(p.Arg411=) variant causes a synonymous change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0586 in 1,209,450 control chromosomes in the GnomAD database, including 1,525 homozygotes. There are 22,775 hemizygotes in GnomAD. In-silico tool predicts a benign outcome for this variant. Variant has been reported in Lovd as Benign (no stars).

Frequency

Genomes: 𝑓 0.055 ( 149 hom., 1680 hem., cov: 22)

Exomes 𝑓: 0.059 ( 1376 hom. 21095 hem. )

Consequence

IRS4
NM_001379150.1 synonymous

Scores

Clinical Significance

Not reported in ClinVar

Conservation

PhyloP100: 0.435

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:

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ACMG classification

Classification made for transcript

Verdict is Benign. Variant got -14 ACMG points.

BP4

Computational evidence support a benign effect (BayesDel_noAF=-0.85).

BP6

Variant X-108735112-T-A is Benign according to our data. Variant chrX-108735112-T-A is described in Lovd as [Benign].

BP7

Synonymous conserved (PhyloP=0.435 with no splicing effect.

BA1

GnomAd4 highest subpopulation (AMR) allele frequency at 95% confidence interval = 0.0724 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein
IRS4	NM_001379150.1 linkuse as main transcript	c.1233A>T	p.Arg411=	synonymous_variant	1/2	ENST00000372129.4	NP_001366079.1
IRS4	NM_003604.2 linkuse as main transcript	c.1233A>T	p.Arg411=	synonymous_variant	1/1		NP_003595.1
IRS4	XM_011531061.2 linkuse as main transcript	c.1233A>T	p.Arg411=	synonymous_variant	1/3		XP_011529363.1
IRS4	XM_006724713.4 linkuse as main transcript	c.1233A>T	p.Arg411=	synonymous_variant	1/2		XP_006724776.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
IRS4	ENST00000372129.4 linkuse as main transcript	c.1233A>T	p.Arg411=	synonymous_variant	1/2		NM_001379150.1	ENSP00000361202	A2
IRS4	ENST00000564206.2 linkuse as main transcript	c.1233A>T	p.Arg411=	synonymous_variant	1/1			ENSP00000505547	P5

Frequencies

GnomAD3 genomes

AF:

0.0551

AC:

6135

AN:

111404

Hom.:

148

Cov.:

AF XY:

0.0498

AC XY:

1674

AN XY:

33620

show subpopulations

Gnomad AFR

AF:

0.0507

Gnomad AMI

AF:

0.0162

Gnomad AMR

AF:

0.0765

Gnomad ASJ

AF:

0.0409

Gnomad EAS

AF:

0.00113

Gnomad SAS

AF:

0.0569

Gnomad FIN

AF:

0.0362

Gnomad MID

AF:

0.0638

Gnomad NFE

AF:

0.0598

Gnomad OTH

AF:

0.0676

GnomAD3 exomes

AF:

0.0540

AC:

9871

AN:

182632

Hom.:

214

AF XY:

0.0515

AC XY:

3463

AN XY:

67272

show subpopulations

Gnomad AFR exome

AF:

0.0545

Gnomad AMR exome

AF:

0.0838

Gnomad ASJ exome

AF:

0.0429

Gnomad EAS exome

AF:

0.000505

Gnomad SAS exome

AF:

0.0594

Gnomad FIN exome

AF:

0.0304

Gnomad NFE exome

AF:

0.0576

Gnomad OTH exome

AF:

0.0522

GnomAD4 exome

AF:

0.0589

AC:

64701

AN:

1097991

Hom.:

1376

Cov.:

AF XY:

0.0581

AC XY:

21095

AN XY:

363383

show subpopulations

Gnomad4 AFR exome

AF:

0.0512

Gnomad4 AMR exome

AF:

0.0815

Gnomad4 ASJ exome

AF:

0.0406

Gnomad4 EAS exome

AF:

0.000199

Gnomad4 SAS exome

AF:

0.0583

Gnomad4 FIN exome

AF:

0.0325

Gnomad4 NFE exome

AF:

0.0623

Gnomad4 OTH exome

AF:

0.0556

GnomAD4 genome

AF:

0.0551

AC:

6144

AN:

111459

Hom.:

149

Cov.:

AF XY:

0.0499

AC XY:

1680

AN XY:

33685

show subpopulations

Gnomad4 AFR

AF:

0.0507

Gnomad4 AMR

AF:

0.0767

Gnomad4 ASJ

AF:

0.0409

Gnomad4 EAS

AF:

0.00114

Gnomad4 SAS

AF:

0.0578

Gnomad4 FIN

AF:

0.0362

Gnomad4 NFE

AF:

0.0598

Gnomad4 OTH

AF:

0.0668

Alfa

AF:

0.0300

Hom.:

220

Bravo

AF:

0.0575

EpiCase

AF:

0.0608

EpiControl

AF:

0.0590

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

BayesDel_noAF

Benign

-0.85

CADD

Benign

5.1

DANN

Benign

0.80

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