16-55326137-A-AAATGCGT

Position:

• chr16-55326137-A-AAATGCGT

Variant summary

Our verdict is Benign. Variant got -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

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 -8 ACMG points.

• BA1: GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.816 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
IRX6	NM_024335.3	c.46-199_46-198insAATGCGT		intron_variant		ENST00000290552.8	NP_077311.2
IRX6	XM_005256137.4	c.46-199_46-198insAATGCGT		intron_variant			XP_005256194.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
IRX6	ENST00000290552.8	c.46-199_46-198insAATGCGT		intron_variant		1	NM_024335.3	ENSP00000290552.8
IRX6	ENST00000558315.1	n.211+127_211+128insAATGCGT		intron_variant		1
ENSG00000259283	ENST00000558730.2	n.88+7363_88+7364insACGCATT		intron_variant		3

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

Gnomad4 AFR exome AF: 0.699

Gnomad4 AMR exome AF: 0.756

Gnomad4 ASJ exome AF: 0.712

Gnomad4 EAS exome AF: 0.841

Gnomad4 SAS exome AF: 0.781

Gnomad4 FIN exome AF: 0.762

Gnomad4 NFE exome AF: 0.741

Gnomad4 OTH exome AF: 0.736

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

Gnomad4 AFR AF: 0.711

Gnomad4 AMR AF: 0.759

Gnomad4 ASJ AF: 0.697

Gnomad4 EAS AF: 0.837

Gnomad4 SAS AF: 0.783

Gnomad4 FIN AF: 0.767

Gnomad4 NFE AF: 0.740

Gnomad4 OTH AF: 0.724

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 v4.3

Splicing

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

Publications

LitVar

Other links and lift over

dbSNP: rs2067217; hg19: chr16-55360049;