16-54930964-A-G

Variant names:

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

Variant summary

Our verdict is Benign. Variant got -20 ACMG points: 0P and 20B. BP4_Strong BP6_Very_Strong BA1

The NM_005853.6(IRX5):​c.-235A>G variant causes a 5 prime UTR change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.741 in 153,242 control chromosomes in the GnomAD database, including 42,618 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★★).

• Frequency:
  • Genomes: 𝑓 0.74 (41724 hom., cov: 30)
  • Exomes 𝑓: 0.77 (894 hom.)
• Consequence: IRX5 NM_005853.6 5_prime_UTR
• Clinical Significance: Benign criteria provided, multiple submitters, no conflicts B:2
• 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 Benign. Variant got -20 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.81).
• BP6: Variant 16-54930964-A-G is Benign according to our data. Variant chr16-54930964-A-G is described in ClinVar as [Benign]. Clinvar id is 1251399.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars.
• BA1: GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.956 is higher than 0.05.

Transcripts

RefSeq

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

Ensembl

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

Frequencies

GnomAD3 genomes AF: 0.740 AC: 111217 AN: 150196 Hom.: 41731 Cov.: 30

Gnomad AFR AF: 0.611

Gnomad AMI AF: 0.715

Gnomad AMR AF: 0.753

Gnomad ASJ AF: 0.831

Gnomad EAS AF: 0.980

Gnomad SAS AF: 0.759

Gnomad FIN AF: 0.781

Gnomad MID AF: 0.795

Gnomad NFE AF: 0.786

Gnomad OTH AF: 0.763

GnomAD4 exome AF: 0.774 AC: 2275 AN: 2940 Hom.: 894 Cov.: 2 AF XY: 0.769 AC XY: 1330 AN XY: 1730

Gnomad4 AFR exome AF: 0.625

Gnomad4 AMR exome AF: 0.758

Gnomad4 ASJ exome AF: 0.729

Gnomad4 EAS exome AF: 0.977

Gnomad4 SAS exome AF: 0.758

Gnomad4 FIN exome AF: 0.780

Gnomad4 NFE exome AF: 0.775

Gnomad4 OTH exome AF: 0.766

GnomAD4 genome AF: 0.740 AC: 111244 AN: 150302 Hom.: 41724 Cov.: 30 AF XY: 0.741 AC XY: 54397 AN XY: 73398

Gnomad4 AFR AF: 0.610

Gnomad4 AMR AF: 0.752

Gnomad4 ASJ AF: 0.831

Gnomad4 EAS AF: 0.979

Gnomad4 SAS AF: 0.758

Gnomad4 FIN AF: 0.781

Gnomad4 NFE AF: 0.786

Gnomad4 OTH AF: 0.766

Alfa AF: 0.684 Hom.: 2088

Bravo AF: 0.736

Asia WGS AF: 0.848 AC: 2821 AN: 3330

ClinVar

Significance: Benign

Submissions summary: Benign:2

Revision: criteria provided, multiple submitters, no conflicts

Submissions by phenotype

not provided Benign:2

Nov 12, 2018

GeneDx

Significance: Benign

Review Status: criteria provided, single submitter

Collection Method: clinical testing

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Breakthrough Genomics, Breakthrough Genomics

Significance: Benign

Review Status: criteria provided, single submitter

Collection Method: not provided

- -

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.81
CADD	Benign	4.7
DANN	Benign	0.49

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;