rs31087

chr16-55329326-G-A

Variant summary

Our verdict is Benign. Variant got -12 ACMG points: 0P and 12B. BP4_Strong BA1

The NM_024335.3(IRX6):c.1333+15G>A variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.349 in 1,582,520 control chromosomes in the GnomAD database, including 98,073 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 0.31 (7805 hom., cov: 32)
  • Exomes 𝑓: 0.35 (90268 hom.)
• Consequence: IRX6 NM_024335.3 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 0.254

Genes affected

IRX6 (HGNC:14675): (iroquois homeobox 6) Predicted to enable DNA-binding transcription activator activity, RNA polymerase II-specific; DNA-binding transcription repressor 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, DNA-templated. Predicted to act upstream of or within detection of visible light; negative regulation of transcription, DNA-templated; and retina morphogenesis in camera-type eye. Predicted to be part of chromatin. Predicted to be active in nucleus. [provided by Alliance of Genome Resources, Apr 2022]

(HGNC:):

ACMG classification

Verdict is Benign. Variant got -12 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.86).
• BA1: GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.453 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
IRX6	NM_024335.3	c.1333+15G>A		intron_variant		ENST00000290552.8
IRX6	XM_005256137.4	c.1333+15G>A		intron_variant

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
IRX6	ENST00000290552.8	c.1333+15G>A		intron_variant		1	NM_024335.3	P1
	ENST00000558730.2	n.88+4175C>T		intron_variant, non_coding_transcript_variant		3

Frequencies

GnomAD3 genomes AF: 0.315 AC: 47808 AN: 151904 Hom.: 7804 Cov.: 32

Gnomad AFR AF: 0.229

Gnomad AMI AF: 0.352

Gnomad AMR AF: 0.300

Gnomad ASJ AF: 0.310

Gnomad EAS AF: 0.469

Gnomad SAS AF: 0.380

Gnomad FIN AF: 0.372

Gnomad MID AF: 0.263

Gnomad NFE AF: 0.345

Gnomad OTH AF: 0.318

GnomAD3 exomes AF: 0.352 AC: 81466 AN: 231570 Hom.: 14574 AF XY: 0.353 AC XY: 44796 AN XY: 127042

Gnomad AFR exome AF: 0.228

Gnomad AMR exome AF: 0.320

Gnomad ASJ exome AF: 0.325

Gnomad EAS exome AF: 0.488

Gnomad SAS exome AF: 0.367

Gnomad FIN exome AF: 0.382

Gnomad NFE exome AF: 0.350

Gnomad OTH exome AF: 0.349

GnomAD4 exome AF: 0.353 AC: 505194 AN: 1430498 Hom.: 90268 Cov.: 45 AF XY: 0.353 AC XY: 250181 AN XY: 707986

Gnomad4 AFR exome AF: 0.222

Gnomad4 AMR exome AF: 0.320

Gnomad4 ASJ exome AF: 0.318

Gnomad4 EAS exome AF: 0.457

Gnomad4 SAS exome AF: 0.363

Gnomad4 FIN exome AF: 0.378

Gnomad4 NFE exome AF: 0.354

Gnomad4 OTH exome AF: 0.346

GnomAD4 genome AF: 0.315 AC: 47835 AN: 152022 Hom.: 7805 Cov.: 32 AF XY: 0.315 AC XY: 23430 AN XY: 74298

Gnomad4 AFR AF: 0.229

Gnomad4 AMR AF: 0.300

Gnomad4 ASJ AF: 0.310

Gnomad4 EAS AF: 0.469

Gnomad4 SAS AF: 0.379

Gnomad4 FIN AF: 0.372

Gnomad4 NFE AF: 0.345

Gnomad4 OTH AF: 0.322

Alfa AF: 0.319 Hom.: 1450

Bravo AF: 0.307

Asia WGS AF: 0.406 AC: 1413 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.86
Cadd	Benign	4.6
Dann	Benign	0.83

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: rs31087; hg19: chr16-55363238; COSMIC: COSV51860821; COSMIC: COSV51860821;