5-1879271-G-C

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.736+233C>G variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.25 in 152,096 control chromosomes in the GnomAD database, including 4,881 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★).

• Frequency: Genomes: 𝑓 0.25 (4881 hom., cov: 33)
• Consequence: IRX4 NM_016358.3 intron
• Clinical Significance: Benign criteria provided, single submitter B:1
• Conservation: PhyloP100: -2.16

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=-1.0).
• BP6: Variant 5-1879271-G-C is Benign according to our data. Variant chr5-1879271-G-C is described in ClinVar as [Benign]. Clinvar id is 1243402.Status of the report is criteria_provided_single_submitter, 1 stars.
• BA1: GnomAd4 highest subpopulation (AMR) allele frequency at 95% confidence interval = 0.296 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
IRX4	NM_016358.3	c.736+233C>G		intron_variant		ENST00000231357.7

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
IRX4	ENST00000231357.7	c.736+233C>G		intron_variant		1	NM_016358.3	P1

Frequencies

GnomAD3 genomes AF: 0.251 AC: 38075 AN: 151976 Hom.: 4879 Cov.: 33

Gnomad AFR AF: 0.271

Gnomad AMI AF: 0.298

Gnomad AMR AF: 0.304

Gnomad ASJ AF: 0.224

Gnomad EAS AF: 0.302

Gnomad SAS AF: 0.255

Gnomad FIN AF: 0.217

Gnomad MID AF: 0.282

Gnomad NFE AF: 0.228

Gnomad OTH AF: 0.245

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

GnomAD4 genome AF: 0.250 AC: 38097 AN: 152096 Hom.: 4881 Cov.: 33 AF XY: 0.250 AC XY: 18628 AN XY: 74368

Gnomad4 AFR AF: 0.271

Gnomad4 AMR AF: 0.303

Gnomad4 ASJ AF: 0.224

Gnomad4 EAS AF: 0.302

Gnomad4 SAS AF: 0.256

Gnomad4 FIN AF: 0.217

Gnomad4 NFE AF: 0.228

Gnomad4 OTH AF: 0.246

Alfa AF: 0.109 Hom.: 162

Bravo AF: 0.258

Asia WGS AF: 0.266 AC: 924 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

- -

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-1.0
Cadd	Benign	0.92
Dann	Benign	0.41

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: rs10475119; hg19: chr5-1879385;