chr5-150848053-G-A

Position:

• chr5-150848053-G-A

Variant summary

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

The NM_001145805.2(IRGM):​c.-71G>A variant causes a 5 prime UTR change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.114 in 1,231,878 control chromosomes in the GnomAD database, including 12,014 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 (2928 hom., cov: 32)
  • Exomes 𝑓: 0.11 (9086 hom.)
• Consequence: IRGM NM_001145805.2 5_prime_UTR
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.104

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=-1.02).
• 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	UniProt
IRGM	NM_001145805.2	c.-71G>A		5_prime_UTR_variant	2/2	ENST00000522154.2
IRGM	NM_001346557.2	c.-71G>A		5_prime_UTR_variant	2/4
IRGM	NR_170598.1	n.1045G>A		non_coding_transcript_exon_variant	2/5

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
IRGM	ENST00000522154.2	c.-71G>A		5_prime_UTR_variant	2/2	1	NM_001145805.2	P1

Frequencies

GnomAD3 genomes AF: 0.165 AC: 25087 AN: 151918 Hom.: 2930 Cov.: 32

Gnomad AFR AF: 0.296

Gnomad AMI AF: 0.0351

Gnomad AMR AF: 0.143

Gnomad ASJ AF: 0.164

Gnomad EAS AF: 0.432

Gnomad SAS AF: 0.207

Gnomad FIN AF: 0.0825

Gnomad MID AF: 0.203

Gnomad NFE AF: 0.0815

Gnomad OTH AF: 0.178

GnomAD4 exome AF: 0.107 AC: 115142 AN: 1079842 Hom.: 9086 Cov.: 14 AF XY: 0.109 AC XY: 58140 AN XY: 533932

Gnomad4 AFR exome AF: 0.305

Gnomad4 AMR exome AF: 0.135

Gnomad4 ASJ exome AF: 0.170

Gnomad4 EAS exome AF: 0.388

Gnomad4 SAS exome AF: 0.197

Gnomad4 FIN exome AF: 0.0829

Gnomad4 NFE exome AF: 0.0792

Gnomad4 OTH exome AF: 0.141

GnomAD4 genome AF: 0.165 AC: 25103 AN: 152036 Hom.: 2928 Cov.: 32 AF XY: 0.166 AC XY: 12354 AN XY: 74326

Gnomad4 AFR AF: 0.296

Gnomad4 AMR AF: 0.142

Gnomad4 ASJ AF: 0.164

Gnomad4 EAS AF: 0.433

Gnomad4 SAS AF: 0.205

Gnomad4 FIN AF: 0.0825

Gnomad4 NFE AF: 0.0815

Gnomad4 OTH AF: 0.179

Alfa AF: 0.0323 Hom.: 34

Bravo AF: 0.177

Asia WGS AF: 0.301 AC: 1047 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	4.5
DANN	Benign	0.40

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: rs9637870; hg19: chr5-150227615; COSMIC: COSV72988830; COSMIC: COSV72988830;