11-10623052-G-T

Variant names:

• chr11-10623052-G-T
• rs10500729
• NM_130385.4:c.1447+726C>A

Variant summary

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

The NM_130385.4(IRAG1):​c.1447+726C>A variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0866 in 152,194 control chromosomes in the GnomAD database, including 1,525 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 0.087 (1525 hom., cov: 33)
• Consequence: IRAG1 NM_130385.4 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 0.364
• Publications: 1 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=-0.91).
• BA1: GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.261 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

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	IRAG1	NM_130385.4	MANE Select	c.1447+726C>A		intron	N/A	NP_569056.4
	IRAG1	NM_001098579.3		c.1423+726C>A		intron	N/A	NP_001092049.2	Q9Y6F6-9
	IRAG1	NM_001100163.3		c.1174+726C>A		intron	N/A	NP_001093633.1	Q9Y6F6-5

Ensembl Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	IRAG1	ENST00000423302.7	TSL:2 MANE Select	c.1447+726C>A		intron	N/A	ENSP00000412130.2	Q9Y6F6-7
	IRAG1	ENST00000534266.6	TSL:2	c.502+726C>A		intron	N/A	ENSP00000433296.2	Q9Y6F6-6
	IRAG1	ENST00000526414.5	TSL:2	n.676+726C>A		intron	N/A	ENSP00000435658.1	E9PJ61

Frequencies

GnomAD3 genomes AF: 0.0863 AC: 13126 AN: 152076 Hom.: 1512 Cov.: 33

Gnomad AFR AF: 0.265

Gnomad AMI AF: 0.00658

Gnomad AMR AF: 0.0309

Gnomad ASJ AF: 0.00605

Gnomad EAS AF: 0.000193

Gnomad SAS AF: 0.0253

Gnomad FIN AF: 0.0188

Gnomad MID AF: 0.0538

Gnomad NFE AF: 0.0177

Gnomad OTH AF: 0.0650

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

GnomAD4 genome AF: 0.0866 AC: 13180 AN: 152194 Hom.: 1525 Cov.: 33 AF XY: 0.0839 AC XY: 6242 AN XY: 74424

African (AFR) AF: 0.265 AC: 10999 AN: 41476

American (AMR) AF: 0.0308 AC: 471 AN: 15304

Ashkenazi Jewish (ASJ) AF: 0.00605 AC: 21 AN: 3472

East Asian (EAS) AF: 0.000193 AC: 1 AN: 5178

South Asian (SAS) AF: 0.0251 AC: 121 AN: 4822

European-Finnish (FIN) AF: 0.0188 AC: 200 AN: 10612

Middle Eastern (MID) AF: 0.0646 AC: 19 AN: 294

European-Non Finnish (NFE) AF: 0.0177 AC: 1206 AN: 68010

Other (OTH) AF: 0.0643 AC: 136 AN: 2114

Alfa AF: 0.0238 Hom.: 33

Bravo AF: 0.0969

Asia WGS AF: 0.0360 AC: 125 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.91
CADD	Benign	1.1
DANN	Benign	0.45
PhyloP100		0.36
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: rs10500729; hg19: chr11-10644599;