ENST00000522154:c.-875C>T

Variant names:

• chr5-150846761-C-T
• rs12658239
• ENST00000522154:c.-875C>T

Variant summary

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

The ENST00000522154(IRGM):​c.-875C>T variant causes a 5 prime UTR premature start codon gain change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0389 in 152,840 control chromosomes in the GnomAD database, including 194 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 0.039 (193 hom., cov: 32)
  • Exomes 𝑓: 0.035 (1 hom.)
• Consequence: IRGM ENST00000522154 5_prime_UTR_premature_start_codon_gain
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 0.124

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=-0.88).
• BA1: GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.171 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
IRGM	NM_001145805.2	c.-875C>T		5_prime_UTR_premature_start_codon_gain_variant	Exon 1 of 2	ENST00000522154.2	NP_001139277.1
IRGM	NM_001145805.2	c.-875C>T		5_prime_UTR_variant	Exon 1 of 2	ENST00000522154.2	NP_001139277.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
IRGM	ENST00000522154	c.-875C>T		5_prime_UTR_premature_start_codon_gain_variant	Exon 1 of 2	1	NM_001145805.2	ENSP00000428220.1
IRGM	ENST00000522154	c.-875C>T		5_prime_UTR_variant	Exon 1 of 2	1	NM_001145805.2	ENSP00000428220.1
IRGM	ENST00000609660.1	n.-42C>T		upstream_gene_variant		6

Frequencies

GnomAD3 genomes AF: 0.0390 AC: 5926 AN: 152094 Hom.: 194 Cov.: 32

Gnomad AFR AF: 0.0150

Gnomad AMI AF: 0.126

Gnomad AMR AF: 0.0306

Gnomad ASJ AF: 0.0372

Gnomad EAS AF: 0.181

Gnomad SAS AF: 0.0628

Gnomad FIN AF: 0.0324

Gnomad MID AF: 0.101

Gnomad NFE AF: 0.0426

Gnomad OTH AF: 0.0388

GnomAD4 exome AF: 0.0350 AC: 22 AN: 628 Hom.: 1 Cov.: 0 AF XY: 0.0383 AC XY: 18 AN XY: 470

Gnomad4 AFR exome AF: 0.00

Gnomad4 AMR exome AF: 0.00

Gnomad4 ASJ exome AF: 0.00

Gnomad4 EAS exome AF: 0.150

Gnomad4 SAS exome AF: 0.0556

Gnomad4 FIN exome AF: 0.125

Gnomad4 NFE exome AF: 0.0303

Gnomad4 OTH exome AF: 0.00

GnomAD4 genome AF: 0.0389 AC: 5922 AN: 152212 Hom.: 193 Cov.: 32 AF XY: 0.0404 AC XY: 3010 AN XY: 74418

Gnomad4 AFR AF: 0.0151

Gnomad4 AMR AF: 0.0306

Gnomad4 ASJ AF: 0.0372

Gnomad4 EAS AF: 0.181

Gnomad4 SAS AF: 0.0628

Gnomad4 FIN AF: 0.0324

Gnomad4 NFE AF: 0.0425

Gnomad4 OTH AF: 0.0379

Alfa AF: 0.0163 Hom.: 8

Bravo AF: 0.0395

Asia WGS AF: 0.0920 AC: 320 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.88
CADD	Benign	6.1
DANN	Benign	0.36

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: rs12658239; hg19: chr5-150226323;