5-1877907-G-A

Position:

• chr5-1877907-G-A

Variant summary

Our verdict is Benign. Variant got -20 ACMG points: 0P and 20B. BP4_Strong BP6_Very_Strong BA1

The NM_016358.3(IRX4):​c.*62C>T variant causes a 3 prime UTR change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.249 in 1,406,274 control chromosomes in the GnomAD database, including 44,513 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★★).

• Frequency:
  • Genomes: 𝑓 0.26 (5181 hom., cov: 34)
  • Exomes 𝑓: 0.25 (39332 hom.)
• Consequence: IRX4 NM_016358.3 3_prime_UTR
• Clinical Significance: Benign criteria provided, multiple submitters, no conflicts B:2
• Conservation: PhyloP100: -0.125

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 (HGNC:):

ACMG classification

Verdict is Benign. Variant got -20 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.93).
• BP6: Variant 5-1877907-G-A is Benign according to our data. Variant chr5-1877907-G-A is described in ClinVar as [Benign]. Clinvar id is 1257512.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars.
• BA1: GnomAd4 highest subpopulation (AMR) allele frequency at 95% confidence interval = 0.304 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
IRX4	NM_016358.3	c.*62C>T		3_prime_UTR_variant	5/5	ENST00000231357.7	NP_057442.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
IRX4	ENST00000231357	c.*62C>T		3_prime_UTR_variant	5/5	1	NM_016358.3	ENSP00000231357.2

Frequencies

GnomAD3 genomes AF: 0.258 AC: 39292 AN: 152066 Hom.: 5179 Cov.: 34

Gnomad AFR AF: 0.277

Gnomad AMI AF: 0.299

Gnomad AMR AF: 0.311

Gnomad ASJ AF: 0.237

Gnomad EAS AF: 0.302

Gnomad SAS AF: 0.262

Gnomad FIN AF: 0.223

Gnomad MID AF: 0.285

Gnomad NFE AF: 0.238

Gnomad OTH AF: 0.254

GnomAD4 exome AF: 0.248 AC: 310905 AN: 1254092 Hom.: 39332 Cov.: 18 AF XY: 0.249 AC XY: 154581 AN XY: 621342

Gnomad4 AFR exome AF: 0.269

Gnomad4 AMR exome AF: 0.337

Gnomad4 ASJ exome AF: 0.229

Gnomad4 EAS exome AF: 0.325

Gnomad4 SAS exome AF: 0.270

Gnomad4 FIN exome AF: 0.223

Gnomad4 NFE exome AF: 0.242

Gnomad4 OTH exome AF: 0.247

GnomAD4 genome AF: 0.258 AC: 39317 AN: 152182 Hom.: 5181 Cov.: 34 AF XY: 0.258 AC XY: 19167 AN XY: 74394

Gnomad4 AFR AF: 0.277

Gnomad4 AMR AF: 0.311

Gnomad4 ASJ AF: 0.237

Gnomad4 EAS AF: 0.302

Gnomad4 SAS AF: 0.262

Gnomad4 FIN AF: 0.223

Gnomad4 NFE AF: 0.238

Gnomad4 OTH AF: 0.254

Alfa AF: 0.115 Hom.: 188

Bravo AF: 0.266

Asia WGS AF: 0.269 AC: 934 AN: 3478

ClinVar

Significance: Benign

Submissions summary: Benign:2

Revision: criteria provided, multiple submitters, no conflicts

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	Nov 12, 2018	- -

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.93
CADD	Benign	1.8
DANN	Benign	0.71

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: rs2279588; hg19: chr5-1878021; COSMIC: COSV51474608; COSMIC: COSV51474608;