rs72553869

Positions:

• chr5-150848671-T-C
• chr5-150848671-T-G

Variant summary

Our verdict is Likely benign. Variant got -2 ACMG points: 2P and 4B. PM2 BP4_Strong

The NM_001145805.2(IRGM):​c.*2T>C variant causes a 3 prime UTR change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.000263 in 1,509,092 control chromosomes in the GnomAD database, including 1 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 0.0014 (1 hom., cov: 32)
  • Exomes 𝑓: 0.00013 (0 hom.)
• Consequence: IRGM NM_001145805.2 3_prime_UTR
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -1.11

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]

IRGM (HGNC:):

ACMG classification

Verdict is Likely_benign. Variant got -2 ACMG points.

• PM2: Very rare variant in population databases, with high coverage
• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.8).

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
IRGM	NM_001145805.2	c.*2T>C		3_prime_UTR_variant	2/2	ENST00000522154.2	NP_001139277.1
IRGM	NM_001346557.2	c.531+17T>C		intron_variant			NP_001333486.1
IRGM	NR_170598.1	n.1646+17T>C		intron_variant

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
IRGM	ENST00000522154.2	c.*2T>C		3_prime_UTR_variant	2/2	1	NM_001145805.2	ENSP00000428220.1
IRGM	ENST00000520549.1	n.156+17T>C		intron_variant		1		ENSP00000429819.1

Frequencies

GnomAD3 genomes AF: 0.00142 AC: 216 AN: 152212 Hom.: 1 Cov.: 32

Gnomad AFR AF: 0.00417

Gnomad AMI AF: 0.00

Gnomad AMR AF: 0.00235

Gnomad ASJ AF: 0.00

Gnomad EAS AF: 0.00

Gnomad SAS AF: 0.00

Gnomad FIN AF: 0.00

Gnomad MID AF: 0.00

Gnomad NFE AF: 0.00

Gnomad OTH AF: 0.00335

GnomAD3 exomes AF: 0.000364 AC: 46 AN: 126436 Hom.: 0 AF XY: 0.000285 AC XY: 19 AN XY: 66770

Gnomad AFR exome AF: 0.00495

Gnomad AMR exome AF: 0.000302

Gnomad ASJ exome AF: 0.00

Gnomad EAS exome AF: 0.00

Gnomad SAS exome AF: 0.00

Gnomad FIN exome AF: 0.00

Gnomad NFE exome AF: 0.0000204

Gnomad OTH exome AF: 0.00113

GnomAD4 exome AF: 0.000133 AC: 181 AN: 1356762 Hom.: 0 Cov.: 27 AF XY: 0.000105 AC XY: 70 AN XY: 665098

Gnomad4 AFR exome AF: 0.00444

Gnomad4 AMR exome AF: 0.000812

Gnomad4 ASJ exome AF: 0.00

Gnomad4 EAS exome AF: 0.00

Gnomad4 SAS exome AF: 0.00

Gnomad4 FIN exome AF: 0.00

Gnomad4 NFE exome AF: 0.00000285

Gnomad4 OTH exome AF: 0.000321

GnomAD4 genome AF: 0.00142 AC: 216 AN: 152330 Hom.: 1 Cov.: 32 AF XY: 0.00115 AC XY: 86 AN XY: 74476

Gnomad4 AFR AF: 0.00416

Gnomad4 AMR AF: 0.00235

Gnomad4 ASJ AF: 0.00

Gnomad4 EAS AF: 0.00

Gnomad4 SAS AF: 0.00

Gnomad4 FIN AF: 0.00

Gnomad4 NFE AF: 0.00

Gnomad4 OTH AF: 0.00331

Alfa AF: 0.000875 Hom.: 1

Bravo AF: 0.00196

Asia WGS AF: 0.000289 AC: 1 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.80
CADD	Benign	1.6
DANN	Benign	0.68

Splicing

Find out detailed SpliceAI scores and Pangolin per-transcript scores at spliceailookup.broadinstitute.org

Publications

LitVar

Other links and lift over

dbSNP: rs72553869; hg19: chr5-150228233;