Variant chr5-1878326-C-T details in Genebe, Genetics Data Aggregator

Variant summary

Our verdict is Benign. Variant got -21 ACMG points: 0P and 21B. BP4_StrongBP6_Very_StrongBP7BA1

The NM_016358.3(IRX4):c.1203G>A(p.Ala401Ala) variant causes a synonymous change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0905 in 1,558,380 control chromosomes in the GnomAD database, including 7,627 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★★).

Frequency

Genomes: 𝑓 0.12 ( 1612 hom., cov: 34)

Exomes 𝑓: 0.087 ( 6015 hom. )

Consequence

IRX4
NM_016358.3 synonymous

Scores

Clinical Significance

Benign criteria provided, multiple submitters, no conflicts P:1B:2

Conservation

PhyloP100: -2.70

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:

IRX4 (HGNC:):

IRX4 links:

Genome browser will be placed here

ACMG classification

Classification made for transcript

Verdict is Benign. Variant got -21 ACMG points.

BP4

Computational evidence support a benign effect (BayesDel_noAF=-0.78).

BP6

Variant 5-1878326-C-T is Benign according to our data. Variant chr5-1878326-C-T is described in ClinVar as [Benign]. Clinvar id is 1247023.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars.

BP7

Synonymous conserved (PhyloP=-2.7 with no splicing effect.

BA1

GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.233 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
IRX4	NM_016358.3 linkuse as main transcript	c.1203G>A	p.Ala401Ala	synonymous_variant	5/5	ENST00000231357.7	NP_057442.1	P78413-1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
IRX4	ENST00000231357.7 linkuse as main transcript	c.1203G>A	p.Ala401Ala	synonymous_variant	5/5	1	NM_016358.3	ENSP00000231357.2		P78413-1

Frequencies

GnomAD3 genomes

AF:

0.122

AC:

18597

AN:

152116

Hom.:

1607

Cov.:

show subpopulations

Gnomad AFR

AF:

0.237

Gnomad AMI

AF:

0.0538

Gnomad AMR

AF:

0.0772

Gnomad ASJ

AF:

0.116

Gnomad EAS

AF:

0.00385

Gnomad SAS

AF:

0.0600

Gnomad FIN

AF:

0.0626

Gnomad MID

AF:

0.102

Gnomad NFE

AF:

0.0869

Gnomad OTH

AF:

0.111

GnomAD3 exomes

AF:

0.0813

AC:

13068

AN:

160656

Hom.:

715

AF XY:

0.0804

AC XY:

7030

AN XY:

87396

show subpopulations

Gnomad AFR exome

AF:

0.246

Gnomad AMR exome

AF:

0.0518

Gnomad ASJ exome

AF:

0.113

Gnomad EAS exome

AF:

0.00254

Gnomad SAS exome

AF:

0.0670

Gnomad FIN exome

AF:

0.0699

Gnomad NFE exome

AF:

0.0900

Gnomad OTH exome

AF:

0.0843

GnomAD4 exome

AF:

0.0871

AC:

122428

AN:

1406146

Hom.:

6015

Cov.:

AF XY:

0.0860

AC XY:

59731

AN XY:

694594

show subpopulations

Gnomad4 AFR exome

AF:

0.249

Gnomad4 AMR exome

AF:

0.0545

Gnomad4 ASJ exome

AF:

0.108

Gnomad4 EAS exome

AF:

0.00105

Gnomad4 SAS exome

AF:

0.0653

Gnomad4 FIN exome

AF:

0.0682

Gnomad4 NFE exome

AF:

0.0877

Gnomad4 OTH exome

AF:

0.0933

GnomAD4 genome

AF:

0.122

AC:

18630

AN:

152234

Hom.:

1612

Cov.:

AF XY:

0.119

AC XY:

8846

AN XY:

74434

show subpopulations

Gnomad4 AFR

AF:

0.237

Gnomad4 AMR

AF:

0.0772

Gnomad4 ASJ

AF:

0.116

Gnomad4 EAS

AF:

0.00386

Gnomad4 SAS

AF:

0.0601

Gnomad4 FIN

AF:

0.0626

Gnomad4 NFE

AF:

0.0869

Gnomad4 OTH

AF:

0.111

Alfa

AF:

0.0963

Hom.:

355

Bravo

AF:

0.130

Asia WGS

AF:

0.0470

AC:

164

AN:

3478

ClinVar

Significance: Benign

Submissions summary: Pathogenic:1Benign:2

Revision: criteria provided, multiple submitters, no conflicts

LINK: link

Submissions by phenotype

not provided

Benign:2

Benign, criteria provided, single submitter	not provided	Breakthrough Genomics, Breakthrough Genomics	-	- -
Benign, criteria provided, single submitter	clinical testing	GeneDx	Oct 17, 2018	- -

See cases

Pathogenic:1

Pathogenic, no assertion criteria provided

case-control

Cytogenetics- Mohapatra Lab, Banaras Hindu University

- -

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

BayesDel_noAF

Benign

-0.78

CADD

Benign

0.14

DANN

Benign

0.78

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