5-1878098-G-A

Variant summary

Our verdict is Benign. Variant got -15 ACMG points: 0P and 15B. BP4_Strong BP6_Moderate BP7 BA1

The NM_016358.3(IRX4):c.1431C>T(p.Gly477=) variant causes a synonymous change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.136 in 1,534,228 control chromosomes in the GnomAD database, including 15,410 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★).

• Frequency:
  • Genomes: 𝑓 0.12 (1292 hom., cov: 34)
  • Exomes 𝑓: 0.14 (14118 hom.)
• Consequence: IRX4 NM_016358.3 synonymous
• Clinical Significance: Benign criteria provided, single submitter B:1
• Conservation: PhyloP100: -0.165

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]

ACMG classification

Verdict is Benign. Variant got -15 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.84).
• BP6: Variant 5-1878098-G-A is Benign according to our data. Variant chr5-1878098-G-A is described in ClinVar as [Benign]. Clinvar id is 1272678.Status of the report is criteria_provided_single_submitter, 1 stars.
• BP7: Synonymous conserved (PhyloP=-0.165 with no splicing effect.
• BA1: GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.314 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
IRX4	NM_016358.3	c.1431C>T	p.Gly477=	synonymous_variant	5/5	ENST00000231357.7

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
IRX4	ENST00000231357.7	c.1431C>T	p.Gly477=	synonymous_variant	5/5	1	NM_016358.3	P1

Frequencies

GnomAD3 genomes AF: 0.119 AC: 18061 AN: 152170 Hom.: 1292 Cov.: 34

Gnomad AFR AF: 0.0804

Gnomad AMI AF: 0.119

Gnomad AMR AF: 0.0898

Gnomad ASJ AF: 0.0950

Gnomad EAS AF: 0.327

Gnomad SAS AF: 0.183

Gnomad FIN AF: 0.116

Gnomad MID AF: 0.160

Gnomad NFE AF: 0.129

Gnomad OTH AF: 0.129

GnomAD3 exomes AF: 0.142 AC: 19216 AN: 135612 Hom.: 1733 AF XY: 0.145 AC XY: 10803 AN XY: 74252

Gnomad AFR exome AF: 0.0844

Gnomad AMR exome AF: 0.0717

Gnomad ASJ exome AF: 0.0982

Gnomad EAS exome AF: 0.345

Gnomad SAS exome AF: 0.171

Gnomad FIN exome AF: 0.130

Gnomad NFE exome AF: 0.136

Gnomad OTH exome AF: 0.132

GnomAD4 exome AF: 0.138 AC: 190081 AN: 1381942 Hom.: 14118 Cov.: 32 AF XY: 0.139 AC XY: 94569 AN XY: 682012

Gnomad4 AFR exome AF: 0.0788

Gnomad4 AMR exome AF: 0.0762

Gnomad4 ASJ exome AF: 0.105

Gnomad4 EAS exome AF: 0.290

Gnomad4 SAS exome AF: 0.169

Gnomad4 FIN exome AF: 0.130

Gnomad4 NFE exome AF: 0.135

Gnomad4 OTH exome AF: 0.143

GnomAD4 genome AF: 0.119 AC: 18067 AN: 152286 Hom.: 1292 Cov.: 34 AF XY: 0.119 AC XY: 8893 AN XY: 74466

Gnomad4 AFR AF: 0.0804

Gnomad4 AMR AF: 0.0899

Gnomad4 ASJ AF: 0.0950

Gnomad4 EAS AF: 0.327

Gnomad4 SAS AF: 0.182

Gnomad4 FIN AF: 0.116

Gnomad4 NFE AF: 0.129

Gnomad4 OTH AF: 0.129

Alfa AF: 0.118 Hom.: 240

Bravo AF: 0.114

Asia WGS AF: 0.237 AC: 822 AN: 3478

ClinVar

Significance: Benign

Submissions summary: Benign:1

Revision: criteria provided, single submitter

Submissions by phenotype

not provided Benign:1

Benign, criteria provided, single submitter

clinical testing

GeneDx

Aug 16, 2019

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Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.84
Cadd	Benign	3.4
Dann	Benign	0.74

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

Other links and lift over

dbSNP: rs2279589; hg19: chr5-1878212; COSMIC: COSV51472820; COSMIC: COSV51472820;