Variant X-108736282-C-T details in Genebe, Genetics Data Aggregator

Variant summary

Our verdict is Benign. Variant got -19 ACMG points: 0P and 19B. BP4_ModerateBP6_Very_StrongBP7BA1

The NM_001379150.1(IRS4):c.63G>A(p.Ala21=) variant causes a synonymous change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.269 in 1,202,303 control chromosomes in the GnomAD database, including 39,372 homozygotes. There are 102,411 hemizygotes in GnomAD. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★★).

Frequency

Genomes: 𝑓 0.38 ( 7404 hom., 11748 hem., cov: 22)

Exomes 𝑓: 0.26 ( 31968 hom. 90663 hem. )

Consequence

IRS4
NM_001379150.1 synonymous

Scores

Clinical Significance

Benign criteria provided, multiple submitters, no conflicts B:2

Conservation

PhyloP100: -0.671

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:

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ACMG classification

Classification made for transcript

Verdict is Benign. Variant got -19 ACMG points.

BP4

Computational evidence support a benign effect (BayesDel_noAF=-0.46).

BP6

Variant X-108736282-C-T is Benign according to our data. Variant chrX-108736282-C-T is described in ClinVar as [Benign]. Clinvar id is 1300045.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars. Variant chrX-108736282-C-T is described in Lovd as [Benign].

BP7

Synonymous conserved (PhyloP=-0.671 with no splicing effect.

BA1

GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.649 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE
IRS4	NM_001379150.1 linkuse as main transcript	c.63G>A	p.Ala21=	synonymous_variant	1/2	ENST00000372129.4
IRS4	NM_003604.2 linkuse as main transcript	c.63G>A	p.Ala21=	synonymous_variant	1/1
IRS4	XM_011531061.2 linkuse as main transcript	c.63G>A	p.Ala21=	synonymous_variant	1/3
IRS4	XM_006724713.4 linkuse as main transcript	c.63G>A	p.Ala21=	synonymous_variant	1/2

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris
IRS4	ENST00000372129.4 linkuse as main transcript	c.63G>A	p.Ala21=	synonymous_variant	1/2		NM_001379150.1	A2
IRS4-AS1	ENST00000668534.1 linkuse as main transcript	n.192C>T		non_coding_transcript_exon_variant	1/3
IRS4	ENST00000564206.2 linkuse as main transcript	c.63G>A	p.Ala21=	synonymous_variant	1/1			P5
IRS4-AS1	ENST00000608811.1 linkuse as main transcript	n.272C>T		non_coding_transcript_exon_variant	1/2	4

Frequencies

GnomAD3 genomes

AF:

0.377

AC:

41439

AN:

109883

Hom.:

7401

Cov.:

AF XY:

0.362

AC XY:

11696

AN XY:

32313

show subpopulations

Gnomad AFR

AF:

0.656

Gnomad AMI

AF:

0.316

Gnomad AMR

AF:

0.515

Gnomad ASJ

AF:

0.181

Gnomad EAS

AF:

0.662

Gnomad SAS

AF:

0.417

Gnomad FIN

AF:

0.137

Gnomad MID

AF:

0.162

Gnomad NFE

AF:

0.210

Gnomad OTH

AF:

0.360

GnomAD3 exomes

AF:

0.346

AC:

61225

AN:

176758

Hom.:

10409

AF XY:

0.304

AC XY:

19262

AN XY:

63364

show subpopulations

Gnomad AFR exome

AF:

0.653

Gnomad AMR exome

AF:

0.641

Gnomad ASJ exome

AF:

0.181

Gnomad EAS exome

AF:

0.642

Gnomad SAS exome

AF:

0.419

Gnomad FIN exome

AF:

0.137

Gnomad NFE exome

AF:

0.194

Gnomad OTH exome

AF:

0.283

GnomAD4 exome

AF:

0.258

AC:

282352

AN:

1092370

Hom.:

31968

Cov.:

AF XY:

0.253

AC XY:

90663

AN XY:

358512

show subpopulations

Gnomad4 AFR exome

AF:

0.657

Gnomad4 AMR exome

AF:

0.632

Gnomad4 ASJ exome

AF:

0.187

Gnomad4 EAS exome

AF:

0.686

Gnomad4 SAS exome

AF:

0.418

Gnomad4 FIN exome

AF:

0.150

Gnomad4 NFE exome

AF:

0.210

Gnomad4 OTH exome

AF:

0.292

GnomAD4 genome

AF:

0.377

AC:

41499

AN:

109933

Hom.:

7404

Cov.:

AF XY:

0.363

AC XY:

11748

AN XY:

32373

show subpopulations

Gnomad4 AFR

AF:

0.656

Gnomad4 AMR

AF:

0.515

Gnomad4 ASJ

AF:

0.181

Gnomad4 EAS

AF:

0.662

Gnomad4 SAS

AF:

0.418

Gnomad4 FIN

AF:

0.137

Gnomad4 NFE

AF:

0.210

Gnomad4 OTH

AF:

0.358

Alfa

AF:

0.273

Hom.:

2622

Bravo

AF:

0.422

EpiCase

AF:

0.209

EpiControl

AF:

0.200

ClinVar

Significance: Benign

Submissions summary: Benign:2

Revision: criteria provided, multiple submitters, no conflicts

LINK: link

Submissions by phenotype

not provided

Benign:1

Benign, criteria provided, single submitter

not provided

Breakthrough Genomics, Breakthrough Genomics

- -

Hypothyroidism, congenital, nongoitrous, 9

Benign:1

Benign, criteria provided, single submitter

clinical testing

Genome-Nilou Lab

Aug 19, 2021

- -

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

BayesDel_noAF

Benign

-0.46

CADD

Benign

7.0

DANN

Benign

0.95

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