rs10059011

chr5-150847160-A-Cchr5-150847160-A-T

Variant summary

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

The NM_001145805.2(IRGM):c.-476A>C variant causes a 5 prime UTR change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.529 in 152,154 control chromosomes in the GnomAD database, including 21,478 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 0.53 (21444 hom., cov: 31)
  • Exomes 𝑓: 0.58 (34 hom.)
• Consequence: IRGM NM_001145805.2 5_prime_UTR
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.306

Genes affected

IRGM (HGNC:29597): (immunity related GTPase M) This gene encodes a member of the p47 immunity-related GTPase family. The encoded protein may play a role in the innate immune response by regulating autophagy formation in response to intracellular pathogens. Polymorphisms that affect the normal expression of this gene are associated with a susceptibility to Crohn's disease and tuberculosis. Alternative splicing results in multiple transcript variants encoding different isoforms. [provided by RefSeq, Oct 2016]

ACMG classification

Verdict is Benign. Variant got -12 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-1.0).
• BA1: GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.553 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
IRGM	NM_001145805.2	c.-476A>C		5_prime_UTR_variant	1/2	ENST00000522154.2
IRGM	NM_001346557.2	c.-476A>C		5_prime_UTR_variant	1/4
IRGM	NR_170598.1	n.640A>C		non_coding_transcript_exon_variant	1/5

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
IRGM	ENST00000522154.2	c.-476A>C		5_prime_UTR_variant	1/2	1	NM_001145805.2	P1
IRGM	ENST00000609660.1	n.358A>C		non_coding_transcript_exon_variant	1/1

Frequencies

GnomAD3 genomes AF: 0.529 AC: 80286 AN: 151838 Hom.: 21432 Cov.: 31

Gnomad AFR AF: 0.559

Gnomad AMI AF: 0.359

Gnomad AMR AF: 0.421

Gnomad ASJ AF: 0.464

Gnomad EAS AF: 0.442

Gnomad SAS AF: 0.415

Gnomad FIN AF: 0.555

Gnomad MID AF: 0.443

Gnomad NFE AF: 0.551

Gnomad OTH AF: 0.530

GnomAD4 exome AF: 0.581 AC: 115 AN: 198 Hom.: 34 Cov.: 0 AF XY: 0.576 AC XY: 68 AN XY: 118

Gnomad4 ASJ exome AF: 0.750

Gnomad4 EAS exome AF: 0.559

Gnomad4 SAS exome AF: 1.00

Gnomad4 FIN exome AF: 0.750

Gnomad4 NFE exome AF: 0.604

Gnomad4 OTH exome AF: 0.500

GnomAD4 genome AF: 0.529 AC: 80340 AN: 151956 Hom.: 21444 Cov.: 31 AF XY: 0.521 AC XY: 38675 AN XY: 74300

Gnomad4 AFR AF: 0.559

Gnomad4 AMR AF: 0.420

Gnomad4 ASJ AF: 0.464

Gnomad4 EAS AF: 0.442

Gnomad4 SAS AF: 0.414

Gnomad4 FIN AF: 0.555

Gnomad4 NFE AF: 0.551

Gnomad4 OTH AF: 0.529

Alfa AF: 0.532 Hom.: 34052

Bravo AF: 0.520

Asia WGS AF: 0.436 AC: 1515 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-1.0
Cadd	Benign	3.7
Dann	Benign	0.52

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: rs10059011; hg19: chr5-150226722;