16-55326137-A-AAATGCGT

Variant names:

• chr16-55326137-A-AAATGCGT
• rs2067217
• NM_024335.3:c.46-199_46-198insAATGCGT

Variant summary

Our verdict is Benign. The variant received -8 ACMG points: 0P and 8B. BA1

The NM_024335.3(IRX6):​c.46-199_46-198insAATGCGT variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.748 in 594,864 control chromosomes in the GnomAD database, including 166,929 homozygotes. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar.

• Frequency:
  • Genomes: 𝑓 0.74 (41352 hom., cov: 0)
  • Exomes 𝑓: 0.75 (125577 hom.)
• Consequence: IRX6 NM_024335.3 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 0.0310
• Publications: 2 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 -8 ACMG points.

• BA1: GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.816 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.46-199_46-198insAATGCGT		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.46-199_46-198insAATGCGT		intron	N/A	ENSP00000290552.8
	IRX6	ENST00000558315.1	TSL:1	n.211+127_211+128insAATGCGT		intron	N/A
	IRX6	ENST00000944938.1		c.46-199_46-198insAATGCGT		intron	N/A	ENSP00000614997.1

Frequencies

GnomAD3 genomes AF: 0.739 AC: 111655 AN: 151150 Hom.: 41312 Cov.: 0

Gnomad AFR AF: 0.711

Gnomad AMI AF: 0.663

Gnomad AMR AF: 0.758

Gnomad ASJ AF: 0.697

Gnomad EAS AF: 0.837

Gnomad SAS AF: 0.783

Gnomad FIN AF: 0.767

Gnomad MID AF: 0.685

Gnomad NFE AF: 0.740

Gnomad OTH AF: 0.722

GnomAD4 exome AF: 0.751 AC: 333232 AN: 443598 Hom.: 125577 AF XY: 0.753 AC XY: 174475 AN XY: 231564

African (AFR) AF: 0.699 AC: 8681 AN: 12426

American (AMR) AF: 0.756 AC: 12013 AN: 15900

Ashkenazi Jewish (ASJ) AF: 0.712 AC: 9635 AN: 13526

East Asian (EAS) AF: 0.841 AC: 25255 AN: 30022

South Asian (SAS) AF: 0.781 AC: 33184 AN: 42468

European-Finnish (FIN) AF: 0.762 AC: 22315 AN: 29296

Middle Eastern (MID) AF: 0.671 AC: 1295 AN: 1930

European-Non Finnish (NFE) AF: 0.741 AC: 202055 AN: 272500

Other (OTH) AF: 0.736 AC: 18799 AN: 25530

GnomAD4 genome AF: 0.739 AC: 111748 AN: 151266 Hom.: 41352 Cov.: 0 AF XY: 0.741 AC XY: 54724 AN XY: 73886

African (AFR) AF: 0.711 AC: 29304 AN: 41230

American (AMR) AF: 0.759 AC: 11549 AN: 15224

Ashkenazi Jewish (ASJ) AF: 0.697 AC: 2406 AN: 3452

East Asian (EAS) AF: 0.837 AC: 4269 AN: 5098

South Asian (SAS) AF: 0.783 AC: 3760 AN: 4802

European-Finnish (FIN) AF: 0.767 AC: 8068 AN: 10524

Middle Eastern (MID) AF: 0.682 AC: 199 AN: 292

European-Non Finnish (NFE) AF: 0.740 AC: 50083 AN: 67654

Other (OTH) AF: 0.724 AC: 1513 AN: 2090

Alfa AF: 0.657 Hom.: 1849

Bravo AF: 0.736

Asia WGS AF: 0.806 AC: 2805 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
PhyloP100		0.031
Mutation Taster		=31/69	disease causing

Splicing

Find out detailed SpliceAI scores and Pangolin per-transcript scores at spliceailookup.broadinstitute.org

Other links and lift over

dbSNP: rs2067217; hg19: chr16-55360049;