5-150847863-C-T

Position:

• chr5-150847863-C-T

Variant summary

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

The NM_001145805.2(IRGM):​c.-261C>T variant causes a 5 prime UTR change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.143 in 421,450 control chromosomes in the GnomAD database, including 6,606 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 0.17 (2972 hom., cov: 32)
  • Exomes 𝑓: 0.13 (3634 hom.)
• Consequence: IRGM NM_001145805.2 5_prime_UTR
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.299

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=-0.9).
• BA1: GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.418 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
IRGM	NM_001145805.2	c.-261C>T		5_prime_UTR_variant	2/2	ENST00000522154.2	NP_001139277.1
IRGM	NM_001346557.2	c.-261C>T		5_prime_UTR_variant	2/4		NP_001333486.1
IRGM	NR_170598.1	n.855C>T		non_coding_transcript_exon_variant	2/5

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
IRGM	ENST00000522154.2	c.-261C>T		5_prime_UTR_variant	2/2	1	NM_001145805.2	ENSP00000428220	P1

Frequencies

GnomAD3 genomes AF: 0.166 AC: 25219 AN: 151994 Hom.: 2973 Cov.: 32

Gnomad AFR AF: 0.299

Gnomad AMI AF: 0.0351

Gnomad AMR AF: 0.142

Gnomad ASJ AF: 0.163

Gnomad EAS AF: 0.432

Gnomad SAS AF: 0.206

Gnomad FIN AF: 0.0817

Gnomad MID AF: 0.203

Gnomad NFE AF: 0.0815

Gnomad OTH AF: 0.178

GnomAD4 exome AF: 0.130 AC: 35093 AN: 269338 Hom.: 3634 Cov.: 0 AF XY: 0.134 AC XY: 19009 AN XY: 141710

Gnomad4 AFR exome AF: 0.310

Gnomad4 AMR exome AF: 0.134

Gnomad4 ASJ exome AF: 0.174

Gnomad4 EAS exome AF: 0.395

Gnomad4 SAS exome AF: 0.189

Gnomad4 FIN exome AF: 0.0856

Gnomad4 NFE exome AF: 0.0825

Gnomad4 OTH exome AF: 0.142

GnomAD4 genome AF: 0.166 AC: 25237 AN: 152112 Hom.: 2972 Cov.: 32 AF XY: 0.167 AC XY: 12421 AN XY: 74362

Gnomad4 AFR AF: 0.299

Gnomad4 AMR AF: 0.142

Gnomad4 ASJ AF: 0.163

Gnomad4 EAS AF: 0.433

Gnomad4 SAS AF: 0.205

Gnomad4 FIN AF: 0.0817

Gnomad4 NFE AF: 0.0815

Gnomad4 OTH AF: 0.179

Alfa AF: 0.120 Hom.: 210

Bravo AF: 0.178

Asia WGS AF: 0.303 AC: 1053 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.90
CADD	Benign	4.0
DANN	Benign	0.55

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: rs9637876; hg19: chr5-150227425;