16-55325214-A-T

Variant names:

• chr16-55325214-A-T
• rs31078
• NM_024335.3:c.45+78A>T

Variant summary

Our verdict is Benign. The variant received -12 ACMG points: 0P and 12B. BP4_Strong BA1

The ENST00000290552.8(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 ENST00000290552.8 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.362
• Publications: 6 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]

ENSG00000283423 (HGNC:):

ACMG classification

Our verdict: Benign. The variant received -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.

Variant Effect in Transcripts

ACMG analysis was done for transcript: ENST00000290552.8. You can select a different transcript below to see updated ACMG assignments.

RefSeq Transcripts

Selected	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	IRX6	NM_024335.3	MANE Select	c.45+78A>T		intron	N/A	NP_077311.2

Ensembl Transcripts

Selected	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	IRX6	ENST00000290552.8	TSL:1 MANE Select	c.45+78A>T		intron	N/A	ENSP00000290552.8
	ENSG00000283423	ENST00000732786.1		n.49T>A		non_coding_transcript_exon	Exon 1 of 2
	ENSG00000283423	ENST00000732788.1		n.95T>A		non_coding_transcript_exon	Exon 1 of 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

African (AFR) AF: 0.782 AC: 22939 AN: 29348

American (AMR) AF: 0.846 AC: 34950 AN: 41298

Ashkenazi Jewish (ASJ) AF: 0.731 AC: 17852 AN: 24434

East Asian (EAS) AF: 0.888 AC: 34024 AN: 38322

South Asian (SAS) AF: 0.837 AC: 67389 AN: 80556

European-Finnish (FIN) AF: 0.760 AC: 35655 AN: 46932

Middle Eastern (MID) AF: 0.680 AC: 3665 AN: 5388

European-Non Finnish (NFE) AF: 0.750 AC: 691524 AN: 921510

Other (OTH) AF: 0.762 AC: 40470 AN: 53112

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

African (AFR) AF: 0.787 AC: 32581 AN: 41394

American (AMR) AF: 0.794 AC: 12106 AN: 15254

Ashkenazi Jewish (ASJ) AF: 0.719 AC: 2494 AN: 3470

East Asian (EAS) AF: 0.884 AC: 4456 AN: 5040

South Asian (SAS) AF: 0.845 AC: 4046 AN: 4790

European-Finnish (FIN) AF: 0.767 AC: 8084 AN: 10534

Middle Eastern (MID) AF: 0.699 AC: 204 AN: 292

European-Non Finnish (NFE) AF: 0.743 AC: 50453 AN: 67916

Other (OTH) AF: 0.754 AC: 1581 AN: 2098

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 v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.88
CADD	Benign	4.1
DANN	Benign	0.64
PhyloP100		-0.36
Mutation Taster		=100/0	polymorphism (auto)

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

Other links and lift over

dbSNP: rs31078; hg19: chr16-55359126; COSMIC: COSV51862069; COSMIC: COSV51862069;