chr11-10670174-T-C

Variant names:

• chr11-10670174-T-C
• rs1874445
• NM_130385.4:c.68-17992A>G

Variant summary

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

The NM_130385.4(IRAG1):​c.68-17992A>G variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.625 in 152,092 control chromosomes in the GnomAD database, including 30,204 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 0.62 (30204 hom., cov: 33)
• Consequence: IRAG1 NM_130385.4 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.301
• Publications: 9 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=-0.85).
• BA1: GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.949 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
IRAG1	NM_130385.4	c.68-17992A>G		intron_variant	Intron 1 of 20	ENST00000423302.7	NP_569056.4

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
IRAG1	ENST00000423302.7	c.68-17992A>G		intron_variant	Intron 1 of 20	2	NM_130385.4	ENSP00000412130.2
IRAG1	ENST00000526414.5	n.-89-17992A>G		intron_variant	Intron 1 of 16	2		ENSP00000435658.1

Frequencies

GnomAD3 genomes AF: 0.625 AC: 94954 AN: 151974 Hom.: 30195 Cov.: 33

Gnomad AFR AF: 0.610

Gnomad AMI AF: 0.465

Gnomad AMR AF: 0.633

Gnomad ASJ AF: 0.643

Gnomad EAS AF: 0.972

Gnomad SAS AF: 0.763

Gnomad FIN AF: 0.561

Gnomad MID AF: 0.601

Gnomad NFE AF: 0.606

Gnomad OTH AF: 0.643

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

GnomAD4 genome AF: 0.625 AC: 95012 AN: 152092 Hom.: 30204 Cov.: 33 AF XY: 0.625 AC XY: 46474 AN XY: 74364

African (AFR) AF: 0.610 AC: 25275 AN: 41468

American (AMR) AF: 0.633 AC: 9678 AN: 15284

Ashkenazi Jewish (ASJ) AF: 0.643 AC: 2231 AN: 3468

East Asian (EAS) AF: 0.972 AC: 5042 AN: 5188

South Asian (SAS) AF: 0.762 AC: 3679 AN: 4828

European-Finnish (FIN) AF: 0.561 AC: 5942 AN: 10586

Middle Eastern (MID) AF: 0.588 AC: 173 AN: 294

European-Non Finnish (NFE) AF: 0.606 AC: 41212 AN: 67956

Other (OTH) AF: 0.643 AC: 1358 AN: 2112

Alfa AF: 0.614 Hom.: 46436

Bravo AF: 0.632

Asia WGS AF: 0.836 AC: 2901 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.85
CADD	Benign	2.5
DANN	Benign	0.62
PhyloP100		-0.30
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: rs1874445; hg19: chr11-10691721;