11-10666670-A-G

Variant names:

• chr11-10666670-A-G
• rs1425151
• NM_130385.4:c.68-14488T>C

Variant summary

Our verdict is Benign. The variant received -12 ACMG points: 0P and 12B. BP4_Strong BA1

The NM_130385.4(IRAG1):​c.68-14488T>C variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.234 in 152,232 control chromosomes in the GnomAD database, including 5,396 homozygotes. 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 0.23 (5396 hom., cov: 33)
• Consequence: IRAG1 NM_130385.4 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.496
• Publications: 4 publications found

Genes affected

IRAG1 (HGNC:7237): (inositol 1,4,5-triphosphate receptor associated 1) This gene is similar to a putative mouse tumor suppressor gene (Mrvi1) that is frequently disrupted by mouse AIDS-related virus (MRV). The encoded protein, which is found in the membrane of the endoplasmic reticulum, is similar to Jaw1, a lymphoid-restricted protein whose expression is down-regulated during lymphoid differentiation. This protein is a substrate of cGMP-dependent kinase-1 (PKG1) that can function as a regulator of IP3-induced calcium release. Studies in mouse suggest that MRV integration at Mrvi1 induces myeloid leukemia by altering the expression of a gene important for myeloid cell growth and/or differentiation, and thus this gene may function as a myeloid leukemia tumor suppressor gene. Several alternatively spliced transcript variants encoding different isoforms have been found for this gene, and alternative translation start sites, including a non-AUG (CUG) start site, are used. [provided by RefSeq, May 2011]

ACMG classification

Our verdict: Benign. The variant received -12 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.87).
• BA1: GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.792 is higher than 0.05.

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_130385.4. 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
	IRAG1	NM_130385.4	MANE Select	c.68-14488T>C		intron	N/A	NP_569056.4
	IRAG1	NM_001100163.3		c.-49+23595T>C		intron	N/A	NP_001093633.1
	IRAG1	NM_001206880.2		c.68-14488T>C		intron	N/A	NP_001193809.1

Ensembl Transcripts

Selected	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	IRAG1	ENST00000423302.7	TSL:2 MANE Select	c.68-14488T>C		intron	N/A	ENSP00000412130.2
	IRAG1	ENST00000526414.5	TSL:2	n.-89-14488T>C		intron	N/A	ENSP00000435658.1
	IRAG1	ENST00000541483.5	TSL:2	c.68-14488T>C		intron	N/A	ENSP00000437784.1

Frequencies

GnomAD3 genomes AF: 0.234 AC: 35658 AN: 152114 Hom.: 5386 Cov.: 33

Gnomad AFR AF: 0.181

Gnomad AMI AF: 0.0976

Gnomad AMR AF: 0.309

Gnomad ASJ AF: 0.238

Gnomad EAS AF: 0.813

Gnomad SAS AF: 0.388

Gnomad FIN AF: 0.218

Gnomad MID AF: 0.165

Gnomad NFE AF: 0.200

Gnomad OTH AF: 0.219

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

GnomAD4 genome AF: 0.234 AC: 35697 AN: 152232 Hom.: 5396 Cov.: 33 AF XY: 0.242 AC XY: 17977 AN XY: 74436

African (AFR) AF: 0.182 AC: 7543 AN: 41534

American (AMR) AF: 0.310 AC: 4743 AN: 15292

Ashkenazi Jewish (ASJ) AF: 0.238 AC: 827 AN: 3468

East Asian (EAS) AF: 0.813 AC: 4208 AN: 5176

South Asian (SAS) AF: 0.387 AC: 1872 AN: 4832

European-Finnish (FIN) AF: 0.218 AC: 2314 AN: 10604

Middle Eastern (MID) AF: 0.153 AC: 45 AN: 294

European-Non Finnish (NFE) AF: 0.200 AC: 13589 AN: 68012

Other (OTH) AF: 0.222 AC: 467 AN: 2108

Alfa AF: 0.248 Hom.: 2098

Bravo AF: 0.244

Asia WGS AF: 0.538 AC: 1864 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.87
CADD	Benign	0.36
DANN	Benign	0.33
PhyloP100		-0.50
Mutation Taster		=100/0	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: rs1425151; hg19: chr11-10688217;