rs3751723

chr16-54286285-G-T

Variant summary

Our verdict is Benign. Variant got -10 ACMG points: 0P and 10B. BP4_Moderate BA1

The NM_024336.3(IRX3):c.-235C>A variant causes a 5 prime UTR change involving the alteration of a conserved nucleotide. The variant allele was found at a frequency of 0.322 in 998,464 control chromosomes in the GnomAD database, including 53,074 homozygotes. In-silico tool predicts a benign outcome for this variant. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar.

• Frequency:
  • Genomes: 𝑓 0.29 (6817 hom., cov: 32)
  • Exomes 𝑓: 0.33 (46257 hom.)
• Consequence: IRX3 NM_024336.3 5_prime_UTR
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 7.27

Genes affected

IRX3 (HGNC:14360): (iroquois homeobox 3) IRX3 is a member of the Iroquois homeobox gene family (see IRX1; MIM 606197) and plays a role in an early step of neural development (Bellefroid et al., 1998 [PubMed 9427753]). Members of this family appear to play multiple roles during pattern formation of vertebrate embryos (Lewis et al., 1999 [PubMed 10370142]).[supplied by OMIM, Aug 2009]

(HGNC:):

ACMG classification

Verdict is Benign. Variant got -10 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.3).
• BA1: GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.495 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
IRX3	NM_024336.3	c.-235C>A		5_prime_UTR_variant	1/4	ENST00000329734.4
IRX3	XM_005256139.4	c.-235C>A		5_prime_UTR_variant	1/4

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
IRX3	ENST00000329734.4	c.-235C>A		5_prime_UTR_variant	1/4	1	NM_024336.3	P1
	ENST00000637770.1	n.56+626G>T		intron_variant, non_coding_transcript_variant		1
IRX3	ENST00000558180.2	n.46+394C>A		intron_variant, non_coding_transcript_variant		4

Frequencies

GnomAD3 genomes AF: 0.287 AC: 43652 AN: 151834 Hom.: 6821 Cov.: 32

Gnomad AFR AF: 0.159

Gnomad AMI AF: 0.436

Gnomad AMR AF: 0.314

Gnomad ASJ AF: 0.288

Gnomad EAS AF: 0.512

Gnomad SAS AF: 0.379

Gnomad FIN AF: 0.270

Gnomad MID AF: 0.345

Gnomad NFE AF: 0.336

Gnomad OTH AF: 0.321

GnomAD4 exome AF: 0.328 AC: 277871 AN: 846512 Hom.: 46257 Cov.: 34 AF XY: 0.328 AC XY: 128618 AN XY: 392514

Gnomad4 AFR exome AF: 0.149

Gnomad4 AMR exome AF: 0.318

Gnomad4 ASJ exome AF: 0.277

Gnomad4 EAS exome AF: 0.524

Gnomad4 SAS exome AF: 0.357

Gnomad4 FIN exome AF: 0.242

Gnomad4 NFE exome AF: 0.331

Gnomad4 OTH exome AF: 0.331

GnomAD4 genome AF: 0.287 AC: 43653 AN: 151952 Hom.: 6817 Cov.: 32 AF XY: 0.287 AC XY: 21316 AN XY: 74270

Gnomad4 AFR AF: 0.159

Gnomad4 AMR AF: 0.314

Gnomad4 ASJ AF: 0.288

Gnomad4 EAS AF: 0.511

Gnomad4 SAS AF: 0.379

Gnomad4 FIN AF: 0.270

Gnomad4 NFE AF: 0.336

Gnomad4 OTH AF: 0.323

Alfa AF: 0.331 Hom.: 8418

Bravo AF: 0.286

Asia WGS AF: 0.452 AC: 1567 AN: 3476

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.30
Cadd	Benign	19
Dann	Benign	0.97

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: rs3751723; hg19: chr16-54320197; COSMIC: COSV61667968; COSMIC: COSV61667968;