rs33993564

chr5-150846690-CG-Cchr5-150846690-CG-CGG

Variant summary

Our verdict is Benign. Variant got -8 ACMG points: 0P and 8B. BA1

The NM_001145805.2(IRGM):c.-942del variant causes a 5 prime UTR change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.206 in 152,114 control chromosomes in the GnomAD database, including 5,179 homozygotes. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar.

• Frequency:
  • Genomes: 𝑓 0.21 (5179 hom., cov: 28)
  • Exomes 𝑓: 0.037 (0 hom.)
• Consequence: IRGM NM_001145805.2 5_prime_UTR
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 0.00

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 -8 ACMG points.

• BA1: GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.435 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
IRGM	NM_001145805.2	c.-942del		5_prime_UTR_variant	1/2	ENST00000522154.2
IRGM	NM_001346557.2	c.-942del		5_prime_UTR_variant	1/4
IRGM	NR_170598.1	n.174del		non_coding_transcript_exon_variant	1/5

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
IRGM	ENST00000522154.2	c.-942del		5_prime_UTR_variant	1/2	1	NM_001145805.2	P1

Frequencies

GnomAD3 genomes AF: 0.206 AC: 31199 AN: 151650 Hom.: 5165 Cov.: 28

Gnomad AFR AF: 0.441

Gnomad AMI AF: 0.0341

Gnomad AMR AF: 0.154

Gnomad ASJ AF: 0.164

Gnomad EAS AF: 0.431

Gnomad SAS AF: 0.210

Gnomad FIN AF: 0.0809

Gnomad MID AF: 0.203

Gnomad NFE AF: 0.0815

Gnomad OTH AF: 0.209

GnomAD4 exome AF: 0.0374 AC: 13 AN: 348 Hom.: 0 Cov.: 0 AF XY: 0.0338 AC XY: 9 AN XY: 266

Gnomad4 AFR exome AF: 0.250

Gnomad4 ASJ exome AF: 0.250

Gnomad4 EAS exome AF: 0.0625

Gnomad4 SAS exome AF: 0.00

Gnomad4 FIN exome AF: 0.00

Gnomad4 NFE exome AF: 0.0270

Gnomad4 OTH exome AF: 0.00

GnomAD4 genome AF: 0.206 AC: 31250 AN: 151766 Hom.: 5179 Cov.: 28 AF XY: 0.206 AC XY: 15287 AN XY: 74208

Gnomad4 AFR AF: 0.441

Gnomad4 AMR AF: 0.153

Gnomad4 ASJ AF: 0.164

Gnomad4 EAS AF: 0.432

Gnomad4 SAS AF: 0.209

Gnomad4 FIN AF: 0.0809

Gnomad4 NFE AF: 0.0816

Gnomad4 OTH AF: 0.210

Alfa AF: 0.0196 Hom.: 9

Asia WGS AF: 0.321 AC: 1116 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Splicing

Name	Calibrated prediction	Score	Prediction
SpliceAI score (max)		0.020		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: rs33993564; hg19: chr5-150226252;