Variant rs73253702 details in Genebe, Genetics Data Aggregator

Variant summary

Our verdict is Benign. Variant got -12 ACMG points: 0P and 12B. BP4_ModerateBP6BP7BA1

The NM_001379150.1(IRS4):c.138C>T(p.Thr46=) variant causes a synonymous change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0599 in 1,208,224 control chromosomes in the GnomAD database, including 1,589 homozygotes. There are 23,214 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 0.062 ( 182 hom., 1892 hem., cov: 21)

Exomes 𝑓: 0.060 ( 1407 hom. 21322 hem. )

Consequence

IRS4
NM_001379150.1 synonymous

Scores

Clinical Significance

Not reported in ClinVar

Conservation

PhyloP100: 1.52

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:55650): (IRS4 antisense RNA 1)

IRS4-AS1 links:

Genome browser will be placed here

ACMG classification

Classification made for transcript

Verdict is Benign. Variant got -12 ACMG points.

BP4

Computational evidence support a benign effect (BayesDel_noAF=-0.35).

BP6

Variant X-108736207-G-A is Benign according to our data. Variant chrX-108736207-G-A is described in Lovd as [Benign].

BP7

Synonymous conserved (PhyloP=1.52 with no splicing effect.

BA1

GnomAd4 highest subpopulation (AMR) allele frequency at 95% confidence interval = 0.0742 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE
IRS4	NM_001379150.1 linkuse as main transcript	c.138C>T	p.Thr46=	synonymous_variant	1/2	ENST00000372129.4
IRS4	NM_003604.2 linkuse as main transcript	c.138C>T	p.Thr46=	synonymous_variant	1/1
IRS4	XM_011531061.2 linkuse as main transcript	c.138C>T	p.Thr46=	synonymous_variant	1/3
IRS4	XM_006724713.4 linkuse as main transcript	c.138C>T	p.Thr46=	synonymous_variant	1/2

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris
IRS4	ENST00000372129.4 linkuse as main transcript	c.138C>T	p.Thr46=	synonymous_variant	1/2		NM_001379150.1	A2
IRS4-AS1	ENST00000668534.1 linkuse as main transcript	n.117G>A		non_coding_transcript_exon_variant	1/3
IRS4	ENST00000564206.2 linkuse as main transcript	c.138C>T	p.Thr46=	synonymous_variant	1/1			P5
IRS4-AS1	ENST00000608811.1 linkuse as main transcript	n.197G>A		non_coding_transcript_exon_variant	1/2	4

Frequencies

GnomAD3 genomes

AF:

0.0616

AC:

6833

AN:

110991

Hom.:

181

Cov.:

AF XY:

0.0566

AC XY:

1881

AN XY:

33253

show subpopulations

Gnomad AFR

AF:

0.0720

Gnomad AMI

AF:

0.0149

Gnomad AMR

AF:

0.0784

Gnomad ASJ

AF:

0.0432

Gnomad EAS

AF:

0.00115

Gnomad SAS

AF:

0.0569

Gnomad FIN

AF:

0.0365

Gnomad MID

AF:

0.0601

Gnomad NFE

AF:

0.0605

Gnomad OTH

AF:

0.0699

GnomAD3 exomes

AF:

0.0562

AC:

10106

AN:

179974

Hom.:

225

AF XY:

0.0536

AC XY:

3575

AN XY:

66656

show subpopulations

Gnomad AFR exome

AF:

0.0754

Gnomad AMR exome

AF:

0.0860

Gnomad ASJ exome

AF:

0.0446

Gnomad EAS exome

AF:

0.000510

Gnomad SAS exome

AF:

0.0595

Gnomad FIN exome

AF:

0.0305

Gnomad NFE exome

AF:

0.0581

Gnomad OTH exome

AF:

0.0535

GnomAD4 exome

AF:

0.0597

AC:

65480

AN:

1097184

Hom.:

1407

Cov.:

AF XY:

0.0587

AC XY:

21322

AN XY:

363058

show subpopulations

Gnomad4 AFR exome

AF:

0.0735

Gnomad4 AMR exome

AF:

0.0831

Gnomad4 ASJ exome

AF:

0.0424

Gnomad4 EAS exome

AF:

0.000199

Gnomad4 SAS exome

AF:

0.0584

Gnomad4 FIN exome

AF:

0.0325

Gnomad4 NFE exome

AF:

0.0623

Gnomad4 OTH exome

AF:

0.0574

GnomAD4 genome

AF:

0.0617

AC:

6847

AN:

111040

Hom.:

182

Cov.:

AF XY:

0.0568

AC XY:

1892

AN XY:

33312

show subpopulations

Gnomad4 AFR

AF:

0.0721

Gnomad4 AMR

AF:

0.0787

Gnomad4 ASJ

AF:

0.0432

Gnomad4 EAS

AF:

0.00116

Gnomad4 SAS

AF:

0.0578

Gnomad4 FIN

AF:

0.0365

Gnomad4 NFE

AF:

0.0604

Gnomad4 OTH

AF:

0.0690

Alfa

AF:

0.0369

Hom.:

241

Bravo

AF:

0.0645

EpiCase

AF:

0.0609

EpiControl

AF:

0.0608

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

BayesDel_noAF

Benign

-0.35

CADD

Benign

DANN

Benign

0.93

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