chr16-54930964-A-G

Variant names:

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

Variant summary

Our verdict is Benign. The variant received -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
• Publications: 2 publications found

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]

CRNDE (HGNC:37078): (colorectal neoplasia differentially expressed) This gene is transcribed into multiple transcript variants, some of which may function as non-coding RNAs. One of the transcript variants encodes a putative short protein that is localized to the nucleus (PMID:25978564). Expression of this locus is increased in proliferating tissues, including certain tumors such as colorectal adenomas and adenocarcinomas. Transcription from this gene is negatively regulated by insulin and insulin-like growth factors, and may regulate the expression of genes involved in metabolism. [provided by RefSeq, May 2015]

ACMG classification

Our verdict: Benign. The variant received -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 VariationId 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.

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_005853.6. You can select a different transcript below to see updated ACMG assignments.

RefSeq Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	IRX5	NM_005853.6	MANE Select	c.-235A>G		5_prime_UTR	Exon 1 of 3	NP_005844.4
	IRX5	NM_001252197.1		c.-235A>G		upstream_gene	N/A	NP_001239126.1	P78411-2

Ensembl Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	IRX5	ENST00000394636.9	TSL:3 MANE Select	c.-235A>G		5_prime_UTR	Exon 1 of 3	ENSP00000378132.4	P78411-1
	CRNDE	ENST00000750727.1		n.129+262T>C		intron	N/A
	IRX5	ENST00000320990.9	TSL:1	c.-235A>G		upstream_gene	N/A	ENSP00000316250.5	P78411-2

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

African (AFR) AF: 0.625 AC: 25 AN: 40

American (AMR) AF: 0.758 AC: 47 AN: 62

Ashkenazi Jewish (ASJ) AF: 0.729 AC: 35 AN: 48

East Asian (EAS) AF: 0.977 AC: 43 AN: 44

South Asian (SAS) AF: 0.758 AC: 97 AN: 128

European-Finnish (FIN) AF: 0.780 AC: 131 AN: 168

Middle Eastern (MID) AF: 0.750 AC: 6 AN: 8

European-Non Finnish (NFE) AF: 0.775 AC: 1793 AN: 2314

Other (OTH) AF: 0.766 AC: 98 AN: 128

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

African (AFR) AF: 0.610 AC: 25119 AN: 41156

American (AMR) AF: 0.752 AC: 11422 AN: 15182

Ashkenazi Jewish (ASJ) AF: 0.831 AC: 2875 AN: 3460

East Asian (EAS) AF: 0.979 AC: 4861 AN: 4964

South Asian (SAS) AF: 0.758 AC: 3642 AN: 4806

European-Finnish (FIN) AF: 0.781 AC: 7811 AN: 10002

Middle Eastern (MID) AF: 0.797 AC: 231 AN: 290

European-Non Finnish (NFE) AF: 0.786 AC: 53034 AN: 67446

Other (OTH) AF: 0.766 AC: 1601 AN: 2090

Alfa AF: 0.684 Hom.: 2088

Bravo AF: 0.736

Asia WGS AF: 0.848 AC: 2821 AN: 3330

ClinVar

ClinVar submissions

Significance: Benign

Revision: criteria provided, multiple submitters, no conflicts

Pathogenic	VUS	Benign	Condition
-	-	2	not provided (2)

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.81
CADD	Benign	4.7
DANN	Benign	0.49
PhyloP100		-0.61
PromoterAI		-0.059	Neutral
Mutation Taster		=299/1	polymorphism (auto)

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

Other links and lift over

dbSNP: rs13334870; hg19: chr16-54964876;