16-55325214-A-G

Variant names:

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

Variant summary

Our verdict is Likely benign. The variant received -2 ACMG points: 2P and 4B. PM2 BP4_Strong

The NM_024335.3(IRX6):​c.45+78A>G variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant was absent in control chromosomes in GnomAD project. 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: not found (cov: 28)
  • Exomes 𝑓: 0.0 (0 hom.)
  • Failed GnomAD Quality Control
• Consequence: IRX6 NM_024335.3 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: Likely_benign. The variant received -2 ACMG points.

• PM2: Very rare variant in population databases, with high coverage
• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.84).

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

Selected	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	IRX6	NM_024335.3	MANE Select	c.45+78A>G		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>G		intron	N/A	ENSP00000290552.8
	ENSG00000283423	ENST00000732786.1		n.49T>C		non_coding_transcript_exon	Exon 1 of 2
	ENSG00000283423	ENST00000732788.1		n.95T>C		non_coding_transcript_exon	Exon 1 of 3

Frequencies

GnomAD3 genomes Cov.: 28

GnomAD4 exome Data not reliable, filtered out with message: AC0 AF: 0.00 AC: 0 AN: 1242982 Hom.: 0 AF XY: 0.00 AC XY: 0 AN XY: 627576

African (AFR) AF: 0.00 AC: 0 AN: 29384

American (AMR) AF: 0.00 AC: 0 AN: 41320

Ashkenazi Jewish (ASJ) AF: 0.00 AC: 0 AN: 24448

East Asian (EAS) AF: 0.00 AC: 0 AN: 38334

South Asian (SAS) AF: 0.00 AC: 0 AN: 80606

European-Finnish (FIN) AF: 0.00 AC: 0 AN: 47002

Middle Eastern (MID) AF: 0.00 AC: 0 AN: 5396

European-Non Finnish (NFE) AF: 0.00 AC: 0 AN: 923298

Other (OTH) AF: 0.00 AC: 0 AN: 53194

GnomAD4 genome Cov.: 28

Alfa AF: 0.00 Hom.: 2343

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.84
CADD	Benign	4.6
DANN	Benign	0.79
PhyloP100		-0.36

Splicing

Name	Calibrated prediction	Score	Prediction
SpliceAI score (max)		0.010		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;