16-54930964-A-T

Variant names:

• chr16-54930964-A-T
• rs13334870
• NM_005853.6:c.-235A>T

Variant summary

Our verdict is Likely benign. Variant got -2 ACMG points: 2P and 4B. PM2 BP4_Strong

The NM_005853.6(IRX5):​c.-235A>T variant causes a 5 prime UTR change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0000931 in 150,382 control chromosomes in the GnomAD database, with no homozygous occurrence. 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 0.000093 (0 hom., cov: 30)
  • Exomes 𝑓: 0.0 (0 hom.)
  • Failed GnomAD Quality Control
• Consequence: IRX5 NM_005853.6 5_prime_UTR
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.611

Genes affected

IRX5 (HGNC:14361): (iroquois homeobox 5) This gene encodes a member of the iroquois homeobox gene family, which are involved in several embryonic developmental processes. Knockout mice lacking this gene show that it is required for retinal cone bipolar cell differentiation, and that it negatively regulates potassium channel gene expression in the heart to ensure coordinated cardiac repolarization. Alternatively spliced transcript variants encoding different isoforms have been found for this gene. [provided by RefSeq, Nov 2011]

ACMG classification

Verdict is Likely_benign. Variant got -2 ACMG points.

• PM2: Very rare variant in population databases, with high coverage
• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.8).

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
IRX5	NM_005853.6	c.-235A>T		5_prime_UTR_variant	Exon 1 of 3	ENST00000394636.9	NP_005844.4
IRX5	NM_001252197.1	c.-235A>T		upstream_gene_variant			NP_001239126.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
IRX5	ENST00000394636	c.-235A>T		5_prime_UTR_variant	Exon 1 of 3	3	NM_005853.6	ENSP00000378132.4
IRX5	ENST00000320990.9	c.-235A>T		upstream_gene_variant		1		ENSP00000316250.5
IRX5	ENST00000560154.5	c.-235A>T		upstream_gene_variant		5		ENSP00000453660.1

Frequencies

GnomAD3 genomes AF: 0.0000932 AC: 14 AN: 150276 Hom.: 0 Cov.: 30

Gnomad AFR AF: 0.000317

Gnomad AMI AF: 0.00

Gnomad AMR AF: 0.0000660

Gnomad ASJ AF: 0.00

Gnomad EAS AF: 0.00

Gnomad SAS AF: 0.00

Gnomad FIN AF: 0.00

Gnomad MID AF: 0.00

Gnomad NFE AF: 0.00

Gnomad OTH AF: 0.00

GnomAD4 exome Data not reliable, filtered out with message: AC0 AF: 0.00 AC: 0 AN: 2950 Hom.: 0 Cov.: 2 AF XY: 0.00 AC XY: 0 AN XY: 1734

Gnomad4 AFR exome AF: 0.00

Gnomad4 AMR exome AF: 0.00

Gnomad4 ASJ exome AF: 0.00

Gnomad4 EAS exome AF: 0.00

Gnomad4 SAS exome AF: 0.00

Gnomad4 FIN exome AF: 0.00

Gnomad4 NFE exome AF: 0.00

Gnomad4 OTH exome AF: 0.00

GnomAD4 genome AF: 0.0000931 AC: 14 AN: 150382 Hom.: 0 Cov.: 30 AF XY: 0.0000681 AC XY: 5 AN XY: 73444

Gnomad4 AFR AF: 0.000316

Gnomad4 AMR AF: 0.0000659

Gnomad4 ASJ AF: 0.00

Gnomad4 EAS AF: 0.00

Gnomad4 SAS AF: 0.00

Gnomad4 FIN AF: 0.00

Gnomad4 NFE AF: 0.00

Gnomad4 OTH AF: 0.00

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.80
CADD	Benign	3.9
DANN	Benign	0.65

Splicing

Name	Calibrated prediction	Score	Prediction
SpliceAI score (max)		0.0		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: rs13334870; hg19: chr16-54964876;