rs10051804

Positions:

• chr5-150846862-T-C

Variant summary

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

The NM_001145805.2(IRGM):​c.-774T>C 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 153,410 control chromosomes in the GnomAD database, including 5,268 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 (5248 hom., cov: 32)
  • Exomes 𝑓: 0.11 (20 hom.)
• Consequence: IRGM NM_001145805.2 5_prime_UTR
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -1.45

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=-0.91).
• BA1: GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.438 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
IRGM	NM_001145805.2	c.-774T>C		5_prime_UTR_variant	1/2	ENST00000522154.2	NP_001139277.1
IRGM	NM_001346557.2	c.-774T>C		5_prime_UTR_variant	1/4		NP_001333486.1
IRGM	NR_170598.1	n.342T>C		non_coding_transcript_exon_variant	1/5

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
IRGM	ENST00000522154.2	c.-774T>C		5_prime_UTR_variant	1/2	1	NM_001145805.2	ENSP00000428220	P1
IRGM	ENST00000609660.1	n.60T>C		non_coding_transcript_exon_variant	1/1

Frequencies

GnomAD3 genomes AF: 0.207 AC: 31449 AN: 151912 Hom.: 5234 Cov.: 32

Gnomad AFR AF: 0.443

Gnomad AMI AF: 0.0351

Gnomad AMR AF: 0.154

Gnomad ASJ AF: 0.164

Gnomad EAS AF: 0.434

Gnomad SAS AF: 0.211

Gnomad FIN AF: 0.0820

Gnomad MID AF: 0.201

Gnomad NFE AF: 0.0819

Gnomad OTH AF: 0.211

GnomAD4 exome AF: 0.111 AC: 153 AN: 1378 Hom.: 20 Cov.: 0 AF XY: 0.116 AC XY: 121 AN XY: 1040

Gnomad4 AFR exome AF: 0.433

Gnomad4 AMR exome AF: 0.111

Gnomad4 ASJ exome AF: 0.208

Gnomad4 EAS exome AF: 0.229

Gnomad4 SAS exome AF: 0.233

Gnomad4 FIN exome AF: 0.0357

Gnomad4 NFE exome AF: 0.0819

Gnomad4 OTH exome AF: 0.141

GnomAD4 genome AF: 0.207 AC: 31501 AN: 152032 Hom.: 5248 Cov.: 32 AF XY: 0.207 AC XY: 15405 AN XY: 74336

Gnomad4 AFR AF: 0.443

Gnomad4 AMR AF: 0.154

Gnomad4 ASJ AF: 0.164

Gnomad4 EAS AF: 0.435

Gnomad4 SAS AF: 0.210

Gnomad4 FIN AF: 0.0820

Gnomad4 NFE AF: 0.0819

Gnomad4 OTH AF: 0.212

Alfa AF: 0.145 Hom.: 378

Bravo AF: 0.224

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.91
CADD	Benign	4.6
DANN	Benign	0.20

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: rs10051804; hg19: chr5-150226424;