5-1878995-A-ATT

Variant summary

Our verdict is Benign. Variant got -10 ACMG points: 0P and 10B. BP6_Moderate BA1

The NM_016358.3(IRX4):c.737-204_737-203insAA variant causes a intron change involving the alteration of a non-conserved nucleotide. Variant has been reported in ClinVar as Benign (★).

• Frequency: Genomes: 𝑓 0.13 (1508 hom., cov: 0)
• Consequence: IRX4 NM_016358.3 intron
• Clinical Significance: Benign criteria provided, single submitter B:1
• Conservation: PhyloP100: -0.720

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 -10 ACMG points.

• BP6: Variant 5-1878995-A-ATT is Benign according to our data. Variant chr5-1878995-A-ATT is described in ClinVar as [Benign]. Clinvar id is 1225866.Status of the report is criteria_provided_single_submitter, 1 stars.
• BA1: GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.32 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
IRX4	NM_016358.3	c.737-204_737-203insAA		intron_variant		ENST00000231357.7

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
IRX4	ENST00000231357.7	c.737-204_737-203insAA		intron_variant		1	NM_016358.3	P1

Frequencies

GnomAD3 genomes AF: 0.133 AC: 19350 AN: 145032 Hom.: 1506 Cov.: 0

Gnomad AFR AF: 0.127

Gnomad AMI AF: 0.120

Gnomad AMR AF: 0.0985

Gnomad ASJ AF: 0.101

Gnomad EAS AF: 0.334

Gnomad SAS AF: 0.201

Gnomad FIN AF: 0.112

Gnomad MID AF: 0.165

Gnomad NFE AF: 0.130

Gnomad OTH AF: 0.135

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

GnomAD4 genome AF: 0.133 AC: 19349 AN: 145058 Hom.: 1508 Cov.: 0 AF XY: 0.134 AC XY: 9448 AN XY: 70408

Gnomad4 AFR AF: 0.127

Gnomad4 AMR AF: 0.0984

Gnomad4 ASJ AF: 0.101

Gnomad4 EAS AF: 0.334

Gnomad4 SAS AF: 0.201

Gnomad4 FIN AF: 0.112

Gnomad4 NFE AF: 0.130

Gnomad4 OTH AF: 0.137

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

Jun 19, 2021

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Computational scores

Source: dbNSFP v4.3

Splicing

Find out detailed SpliceAI scores and Pangolin per-transcript scores at spliceailookup.broadinstitute.org

Publications

LitVar

Other links and lift over

dbSNP: rs546723700; hg19: chr5-1879109;