rs10058943

chr5-150847024-A-G

Variant summary

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

The NM_001145805.2(IRGM):c.-612A>G variant causes a 5 prime UTR change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.207 in 152,318 control chromosomes in the GnomAD database, including 5,253 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 0.21 (5250 hom., cov: 32)
  • Exomes 𝑓: 0.11 (3 hom.)
• Consequence: IRGM NM_001145805.2 5_prime_UTR
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.628

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=-0.89).
• BA1: GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.437 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
IRGM	NM_001145805.2	c.-612A>G		5_prime_UTR_variant	1/2	ENST00000522154.2
IRGM	NM_001346557.2	c.-612A>G		5_prime_UTR_variant	1/4
IRGM	NR_170598.1	n.504A>G		non_coding_transcript_exon_variant	1/5

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
IRGM	ENST00000522154.2	c.-612A>G		5_prime_UTR_variant	1/2	1	NM_001145805.2	P1
IRGM	ENST00000609660.1	n.222A>G		non_coding_transcript_exon_variant	1/1

Frequencies

GnomAD3 genomes AF: 0.207 AC: 31466 AN: 152030 Hom.: 5236 Cov.: 32

Gnomad AFR AF: 0.442

Gnomad AMI AF: 0.0351

Gnomad AMR AF: 0.155

Gnomad ASJ AF: 0.164

Gnomad EAS AF: 0.434

Gnomad SAS AF: 0.211

Gnomad FIN AF: 0.0822

Gnomad MID AF: 0.206

Gnomad NFE AF: 0.0819

Gnomad OTH AF: 0.210

GnomAD4 exome AF: 0.106 AC: 18 AN: 170 Hom.: 3 Cov.: 0 AF XY: 0.125 AC XY: 13 AN XY: 104

Gnomad4 AMR exome AF: 0.00

Gnomad4 EAS exome AF: 0.116

Gnomad4 FIN exome AF: 0.167

Gnomad4 NFE exome AF: 0.0417

GnomAD4 genome AF: 0.207 AC: 31519 AN: 152148 Hom.: 5250 Cov.: 32 AF XY: 0.207 AC XY: 15414 AN XY: 74402

Gnomad4 AFR AF: 0.442

Gnomad4 AMR AF: 0.154

Gnomad4 ASJ AF: 0.164

Gnomad4 EAS AF: 0.435

Gnomad4 SAS AF: 0.210

Gnomad4 FIN AF: 0.0822

Gnomad4 NFE AF: 0.0819

Gnomad4 OTH AF: 0.212

Alfa AF: 0.145 Hom.: 383

Bravo AF: 0.224

Asia WGS AF: 0.322 AC: 1122 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	1.8
Dann	Benign	0.24

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: rs10058943; hg19: chr5-150226586;