5-1879114-C-T

Variant summary

Our verdict is Benign. Variant got -14 ACMG points: 0P and 14B. BP4_Strong BP6_Moderate BA1

The NM_016358.3(IRX4):c.737-322G>A variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.248 in 151,148 control chromosomes in the GnomAD database, including 4,817 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★).

• Frequency: Genomes: 𝑓 0.25 (4817 hom., cov: 31)
• Consequence: IRX4 NM_016358.3 intron
• Clinical Significance: Benign criteria provided, single submitter B:1
• Conservation: PhyloP100: -1.56

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 -14 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.92).
• BP6: Variant 5-1879114-C-T is Benign according to our data. Variant chr5-1879114-C-T is described in ClinVar as [Benign]. Clinvar id is 1257826.Status of the report is criteria_provided_single_submitter, 1 stars.
• BA1: GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.295 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
IRX4	NM_016358.3	c.737-322G>A		intron_variant		ENST00000231357.7

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
IRX4	ENST00000231357.7	c.737-322G>A		intron_variant		1	NM_016358.3	P1

Frequencies

GnomAD3 genomes AF: 0.248 AC: 37529 AN: 151028 Hom.: 4814 Cov.: 31

Gnomad AFR AF: 0.264

Gnomad AMI AF: 0.298

Gnomad AMR AF: 0.303

Gnomad ASJ AF: 0.224

Gnomad EAS AF: 0.303

Gnomad SAS AF: 0.254

Gnomad FIN AF: 0.216

Gnomad MID AF: 0.280

Gnomad NFE AF: 0.228

Gnomad OTH AF: 0.244

We have no GnomAD4 exomes data on this position. Probably position not covered by the project.

GnomAD4 genome AF: 0.248 AC: 37548 AN: 151148 Hom.: 4817 Cov.: 31 AF XY: 0.249 AC XY: 18364 AN XY: 73870

Gnomad4 AFR AF: 0.264

Gnomad4 AMR AF: 0.303

Gnomad4 ASJ AF: 0.224

Gnomad4 EAS AF: 0.304

Gnomad4 SAS AF: 0.255

Gnomad4 FIN AF: 0.216

Gnomad4 NFE AF: 0.228

Gnomad4 OTH AF: 0.245

Alfa AF: 0.235 Hom.: 550

Bravo AF: 0.258

Asia WGS AF: 0.262 AC: 910 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

Nov 12, 2018

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Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.92
Cadd	Benign	1.4
Dann	Benign	0.70

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: rs10475118; hg19: chr5-1879228;