16-55325214-A-T

Position:

• chr16-55325214-A-T

Variant summary

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

The NM_024335.3(IRX6):​c.45+78A>T variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.765 in 1,392,596 control chromosomes in the GnomAD database, including 408,772 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 0.77 (44943 hom., cov: 28)
  • Exomes 𝑓: 0.76 (363829 hom.)
• Consequence: IRX6 NM_024335.3 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.362

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

Verdict is Benign. Variant got -12 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.88).
• BA1: GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.862 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
IRX6	NM_024335.3	c.45+78A>T		intron_variant		ENST00000290552.8	NP_077311.2
IRX6	XM_005256137.4	c.45+78A>T		intron_variant			XP_005256194.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
IRX6	ENST00000290552.8	c.45+78A>T		intron_variant		1	NM_024335.3	ENSP00000290552.8
ENSG00000259283	ENST00000558730.2	n.88+8287T>A		intron_variant		3

Frequencies

GnomAD3 genomes AF: 0.769 AC: 116519 AN: 151578 Hom.: 44907 Cov.: 28

Gnomad AFR AF: 0.787

Gnomad AMI AF: 0.667

Gnomad AMR AF: 0.793

Gnomad ASJ AF: 0.719

Gnomad EAS AF: 0.884

Gnomad SAS AF: 0.845

Gnomad FIN AF: 0.767

Gnomad MID AF: 0.701

Gnomad NFE AF: 0.743

Gnomad OTH AF: 0.751

GnomAD4 exome AF: 0.764 AC: 948468 AN: 1240900 Hom.: 363829 AF XY: 0.766 AC XY: 479825 AN XY: 626518

Gnomad4 AFR exome AF: 0.782

Gnomad4 AMR exome AF: 0.846

Gnomad4 ASJ exome AF: 0.731

Gnomad4 EAS exome AF: 0.888

Gnomad4 SAS exome AF: 0.837

Gnomad4 FIN exome AF: 0.760

Gnomad4 NFE exome AF: 0.750

Gnomad4 OTH exome AF: 0.762

GnomAD4 genome AF: 0.769 AC: 116611 AN: 151696 Hom.: 44943 Cov.: 28 AF XY: 0.771 AC XY: 57151 AN XY: 74098

Gnomad4 AFR AF: 0.787

Gnomad4 AMR AF: 0.794

Gnomad4 ASJ AF: 0.719

Gnomad4 EAS AF: 0.884

Gnomad4 SAS AF: 0.845

Gnomad4 FIN AF: 0.767

Gnomad4 NFE AF: 0.743

Gnomad4 OTH AF: 0.754

Alfa AF: 0.698 Hom.: 2343

Bravo AF: 0.770

Asia WGS AF: 0.878 AC: 3054 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.88
CADD	Benign	4.1
DANN	Benign	0.64

Splicing

Name	Calibrated prediction	Score	Prediction
SpliceAI score (max)		0.040		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: rs31078; hg19: chr16-55359126; COSMIC: COSV51862069; COSMIC: COSV51862069;