16-54931629-C-G

Position:

• chr16-54931629-C-G

Variant summary

Our verdict is Benign. Variant got -14 ACMG points: 0P and 14B. BP4_Strong BP6_Moderate BA1

The NM_005853.6(IRX5):​c.249+182C>G variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.882 in 152,270 control chromosomes in the GnomAD database, including 59,534 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★).

• Frequency: Genomes: 𝑓 0.88 (59534 hom., cov: 35)
• Consequence: IRX5 NM_005853.6 intron
• Clinical Significance: Benign criteria provided, single submitter B:1
• Conservation: PhyloP100: -0.0210

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 -14 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.92).
• BP6: Variant 16-54931629-C-G is Benign according to our data. Variant chr16-54931629-C-G is described in ClinVar as [Benign]. Clinvar id is 1181544.Status of the report is criteria_provided_single_submitter, 1 stars.
• BA1: GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.973 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
IRX5	NM_005853.6	c.249+182C>G		intron_variant		ENST00000394636.9	NP_005844.4
IRX5	XM_011522809.1	c.-542C>G		5_prime_UTR_variant	1/3		XP_011521111.1
IRX5	NM_001252197.1	c.249+182C>G		intron_variant			NP_001239126.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
IRX5	ENST00000394636.9	c.249+182C>G		intron_variant		3	NM_005853.6	ENSP00000378132	A1
IRX5	ENST00000320990.9	c.249+182C>G		intron_variant		1		ENSP00000316250	P4
IRX5	ENST00000560154.5	c.249+182C>G		intron_variant		5		ENSP00000453660

Frequencies

GnomAD3 genomes AF: 0.882 AC: 134132 AN: 152152 Hom.: 59483 Cov.: 35

Gnomad AFR AF: 0.972

Gnomad AMI AF: 0.741

Gnomad AMR AF: 0.839

Gnomad ASJ AF: 0.882

Gnomad EAS AF: 0.996

Gnomad SAS AF: 0.900

Gnomad FIN AF: 0.792

Gnomad MID AF: 0.877

Gnomad NFE AF: 0.842

Gnomad OTH AF: 0.889

We have no GnomAD4 exomes data on this position. Probably position not covered by the project.

GnomAD4 genome AF: 0.882 AC: 134241 AN: 152270 Hom.: 59534 Cov.: 35 AF XY: 0.880 AC XY: 65503 AN XY: 74436

Gnomad4 AFR AF: 0.972

Gnomad4 AMR AF: 0.838

Gnomad4 ASJ AF: 0.882

Gnomad4 EAS AF: 0.996

Gnomad4 SAS AF: 0.900

Gnomad4 FIN AF: 0.792

Gnomad4 NFE AF: 0.842

Gnomad4 OTH AF: 0.890

Alfa AF: 0.800 Hom.: 2397

Bravo AF: 0.888

Asia WGS AF: 0.956 AC: 3324 AN: 3478

ClinVar

Significance: Benign

Submissions summary: Benign:1

Revision: criteria provided, single submitter

Submissions by phenotype

not provided Benign:1

Benign, criteria provided, single submitter

clinical testing

GeneDx

Nov 12, 2018

- -

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.92
CADD	Benign	2.2
DANN	Benign	0.46

Splicing

Name	Calibrated prediction	Score	Prediction
SpliceAI score (max)		0.040		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: rs1136412; hg19: chr16-54965541;