rs31087

Variant names:

• chr16-55329326-G-A
• rs31087
• NM_024335.3:c.1333+15G>A

Variant summary

Our verdict is Benign. The variant received -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
• Publications: 10 publications found

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]

ENSG00000259283 (HGNC:):

ACMG classification

Our verdict: Benign. The variant received -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.

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_024335.3. You can select a different transcript below to see updated ACMG assignments.

RefSeq Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	IRX6	NM_024335.3	MANE Select	c.1333+15G>A		intron	N/A	NP_077311.2

Ensembl Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	IRX6	ENST00000290552.8	TSL:1 MANE Select	c.1333+15G>A		intron	N/A	ENSP00000290552.8
	IRX6	ENST00000944938.1		c.1333+15G>A		intron	N/A	ENSP00000614997.1
	IRX6	ENST00000869145.1		c.1333+15G>A		intron	N/A	ENSP00000539204.1

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

GnomAD2 exomes AF: 0.352 AC: 81466 AN: 231570 AF XY: 0.353

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 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

African (AFR) AF: 0.222 AC: 7305 AN: 32868

American (AMR) AF: 0.320 AC: 13931 AN: 43508

Ashkenazi Jewish (ASJ) AF: 0.318 AC: 8026 AN: 25258

East Asian (EAS) AF: 0.457 AC: 17903 AN: 39142

South Asian (SAS) AF: 0.363 AC: 30957 AN: 85242

European-Finnish (FIN) AF: 0.378 AC: 16496 AN: 43608

Middle Eastern (MID) AF: 0.308 AC: 1735 AN: 5638

European-Non Finnish (NFE) AF: 0.354 AC: 388382 AN: 1096106

Other (OTH) AF: 0.346 AC: 20459 AN: 59128

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

African (AFR) AF: 0.229 AC: 9500 AN: 41500

American (AMR) AF: 0.300 AC: 4581 AN: 15278

Ashkenazi Jewish (ASJ) AF: 0.310 AC: 1078 AN: 3472

East Asian (EAS) AF: 0.469 AC: 2404 AN: 5126

South Asian (SAS) AF: 0.379 AC: 1823 AN: 4806

European-Finnish (FIN) AF: 0.372 AC: 3935 AN: 10580

Middle Eastern (MID) AF: 0.252 AC: 74 AN: 294

European-Non Finnish (NFE) AF: 0.345 AC: 23440 AN: 67948

Other (OTH) AF: 0.322 AC: 681 AN: 2112

Alfa AF: 0.321 Hom.: 2575

Bravo AF: 0.307

Asia WGS AF: 0.406 AC: 1413 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.86
CADD	Benign	4.6
DANN	Benign	0.83
PhyloP100		0.25
Mutation Taster		=100/0	polymorphism (auto)

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

Other links and lift over

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