11-10647681-T-C

Position:

• chr11-10647681-T-C

Variant summary

Our verdict is Benign. Variant got -12 ACMG points: 0P and 12B. BP4_Strong BA1

The NM_130385.4(IRAG1):​c.225+4344A>G variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.78 in 152,122 control chromosomes in the GnomAD database, including 47,527 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 0.78 (47527 hom., cov: 31)
• Consequence: IRAG1 NM_130385.4 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 0.0140

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]

IRAG1 (HGNC:):

ACMG classification

Verdict is Benign. Variant got -12 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.89).
• BA1: GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.959 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
IRAG1	NM_130385.4	c.225+4344A>G		intron_variant		ENST00000423302.7	NP_569056.4

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
IRAG1	ENST00000423302.7	c.225+4344A>G		intron_variant		2	NM_130385.4	ENSP00000412130.2
IRAG1	ENST00000534266.6	c.-671+4344A>G		intron_variant		2		ENSP00000433296.2
IRAG1	ENST00000526414.5	n.69+4344A>G		intron_variant		2		ENSP00000435658.1

Frequencies

GnomAD3 genomes AF: 0.780 AC: 118588 AN: 152004 Hom.: 47475 Cov.: 31

Gnomad AFR AF: 0.944

Gnomad AMI AF: 0.511

Gnomad AMR AF: 0.786

Gnomad ASJ AF: 0.711

Gnomad EAS AF: 0.981

Gnomad SAS AF: 0.849

Gnomad FIN AF: 0.671

Gnomad MID AF: 0.655

Gnomad NFE AF: 0.684

Gnomad OTH AF: 0.775

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

GnomAD4 genome AF: 0.780 AC: 118700 AN: 152122 Hom.: 47527 Cov.: 31 AF XY: 0.781 AC XY: 58103 AN XY: 74354

Gnomad4 AFR AF: 0.944

Gnomad4 AMR AF: 0.786

Gnomad4 ASJ AF: 0.711

Gnomad4 EAS AF: 0.981

Gnomad4 SAS AF: 0.847

Gnomad4 FIN AF: 0.671

Gnomad4 NFE AF: 0.684

Gnomad4 OTH AF: 0.775

Alfa AF: 0.698 Hom.: 40766

Bravo AF: 0.795

Asia WGS AF: 0.914 AC: 3175 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.89
CADD	Benign	2.9
DANN	Benign	0.75

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

Publications

LitVar

Other links and lift over

dbSNP: rs7940646; hg19: chr11-10669228;