Variant 5-1878385-C-A details in Genebe, Genetics Data Aggregator

Variant summary

Our verdict is Benign. Variant got -10 ACMG points: 0P and 10B. BP4_StrongBP6_ModerateBS2

The NM_016358.3(IRX4):c.1144G>T(p.Ala382Ser) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.000713 in 1,476,480 control chromosomes in the GnomAD database, including 6 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 (★).

Frequency

Genomes: 𝑓 0.0036 ( 5 hom., cov: 34)

Exomes 𝑓: 0.00038 ( 1 hom. )

Consequence

IRX4
NM_016358.3 missense

Scores

Clinical Significance

Benign criteria provided, single submitter B:1

Conservation

PhyloP100: 1.18

Variant links:

Genes affected

IRX4 (HGNC:6129): (iroquois homeobox 4) Predicted to enable DNA-binding transcription factor activity, RNA polymerase II-specific and RNA polymerase II cis-regulatory region sequence-specific DNA binding activity. Predicted to be involved in cell development; neuron differentiation; and regulation of transcription by RNA polymerase II. Predicted to act upstream of or within heart development. Predicted to be part of chromatin. Predicted to be active in nucleus. [provided by Alliance of Genome Resources, Apr 2022]

IRX4 links:

Genome browser will be placed here

ACMG classification

Classification made for transcript

Verdict is Benign. Variant got -10 ACMG points.

BP4

Computational evidence support a benign effect (MetaRNN=0.0061333776).

BP6

Variant 5-1878385-C-A is Benign according to our data. Variant chr5-1878385-C-A is described in ClinVar as [Benign]. Clinvar id is 734123.Status of the report is criteria_provided_single_submitter, 1 stars. Variant chr5-1878385-C-A is described in Lovd as [Benign].

BS2

High Homozygotes in GnomAd at 5 gene

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
IRX4	NM_016358.3 linkuse as main transcript	c.1144G>T	p.Ala382Ser	missense_variant	5/5	ENST00000231357.7

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
IRX4	ENST00000231357.7 linkuse as main transcript	c.1144G>T	p.Ala382Ser	missense_variant	5/5	1	NM_016358.3	P1	P78413-1

Frequencies

GnomAD3 genomes

AF:

0.00360

AC:

548

AN:

152014

Hom.:

Cov.:

show subpopulations

Gnomad AFR

AF:

0.0119

Gnomad AMI

AF:

0.00

Gnomad AMR

AF:

0.00275

Gnomad ASJ

AF:

0.00

Gnomad EAS

AF:

0.00

Gnomad SAS

AF:

0.00

Gnomad FIN

AF:

0.00

Gnomad MID

AF:

0.00

Gnomad NFE

AF:

0.0000589

Gnomad OTH

AF:

0.00480

GnomAD3 exomes

AF:

0.00139

AC:

138

AN:

99164

Hom.:

AF XY:

0.00124

AC XY:

AN XY:

54228

show subpopulations

Gnomad AFR exome

AF:

0.0235

Gnomad AMR exome

AF:

0.00156

Gnomad ASJ exome

AF:

0.000167

Gnomad EAS exome

AF:

0.00

Gnomad SAS exome

AF:

0.0000604

Gnomad FIN exome

AF:

0.00

Gnomad NFE exome

AF:

0.00

Gnomad OTH exome

AF:

0.00197

GnomAD4 exome

AF:

0.000378

AC:

500

AN:

1324352

Hom.:

Cov.:

AF XY:

0.000322

AC XY:

209

AN XY:

648854

show subpopulations

Gnomad4 AFR exome

AF:

0.0106

Gnomad4 AMR exome

AF:

0.00195

Gnomad4 ASJ exome

AF:

0.00

Gnomad4 EAS exome

AF:

0.00

Gnomad4 SAS exome

AF:

0.0000285

Gnomad4 FIN exome

AF:

0.00

Gnomad4 NFE exome

AF:

0.0000554

Gnomad4 OTH exome

AF:

0.00136

GnomAD4 genome

AF:

0.00363

AC:

552

AN:

152128

Hom.:

Cov.:

AF XY:

0.00347

AC XY:

258

AN XY:

74368

show subpopulations

Gnomad4 AFR

AF:

0.0119

Gnomad4 AMR

AF:

0.00275

Gnomad4 ASJ

AF:

0.00

Gnomad4 EAS

AF:

0.00

Gnomad4 SAS

AF:

0.00

Gnomad4 FIN

AF:

0.00

Gnomad4 NFE

AF:

0.0000589

Gnomad4 OTH

AF:

0.00475

Alfa

AF:

0.000974

Hom.:

Bravo

AF:

0.00409

ExAC

AF:

0.000470

AC:

ClinVar

Significance: Benign

Submissions summary: Benign:1

Revision: criteria provided, single submitter

LINK: link

Submissions by phenotype

not provided

Benign:1

Benign, criteria provided, single submitter

clinical testing

Invitae

Apr 10, 2018

- -

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

AlphaMissense

Benign

0.075

BayesDel_addAF

Benign

-0.51

BayesDel_noAF

Benign

-0.49

Cadd

Benign

Dann

Uncertain

0.99

DEOGEN2

Benign

0.14

T;T;.;.;T

Eigen

Benign

-0.20

Eigen_PC

Benign

-0.39

FATHMM_MKL

Benign

0.45

MetaRNN

Benign

0.0061

T;T;T;T;T

MetaSVM

Benign

-0.83

MutationAssessor

Benign

-0.55

N;N;.;.;N

MutationTaster

Benign

0.90

N;N;N

PrimateAI

Pathogenic

0.89

PROVEAN

Benign

0.13

N;N;.;.;N

REVEL

Benign

0.13

Sift

Benign

0.090

T;T;.;.;T

Sift4G

Benign

0.73

T;T;T;T;T

Polyphen

0.98

D;D;.;.;D

Vest4

0.13

MVP

0.77

MPC

0.51

ClinPred

0.032

GERP RS

1.3

Varity_R

0.043

gMVP

0.14

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