5-150846783-C-T

Position:

• chr5-150846783-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.-853C>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 0.206 in 153,176 control chromosomes in the GnomAD database, including 5,247 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 (5239 hom., cov: 32)
  • Exomes 𝑓: 0.072 (8 hom.)
• Consequence: IRGM NM_001145805.2 5_prime_UTR_premature_start_codon_gain
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -1.50

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]

IRGM (HGNC:):

ACMG classification

Verdict is Benign. Variant got -12 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.86).
• BA1: GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.437 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
IRGM	NM_001145805.2	c.-853C>T		5_prime_UTR_premature_start_codon_gain_variant	1/2	ENST00000522154.2	NP_001139277.1
IRGM	NM_001145805.2	c.-853C>T		5_prime_UTR_variant	1/2	ENST00000522154.2	NP_001139277.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
IRGM	ENST00000522154	c.-853C>T		5_prime_UTR_premature_start_codon_gain_variant	1/2	1	NM_001145805.2	ENSP00000428220.1
IRGM	ENST00000522154	c.-853C>T		5_prime_UTR_variant	1/2	1	NM_001145805.2	ENSP00000428220.1
IRGM	ENST00000609660.1	n.-20C>T		upstream_gene_variant		6

Frequencies

GnomAD3 genomes AF: 0.207 AC: 31441 AN: 151920 Hom.: 5225 Cov.: 32

Gnomad AFR AF: 0.442

Gnomad AMI AF: 0.0351

Gnomad AMR AF: 0.154

Gnomad ASJ AF: 0.164

Gnomad EAS AF: 0.433

Gnomad SAS AF: 0.211

Gnomad FIN AF: 0.0819

Gnomad MID AF: 0.203

Gnomad NFE AF: 0.0823

Gnomad OTH AF: 0.210

GnomAD4 exome AF: 0.0721 AC: 82 AN: 1138 Hom.: 8 Cov.: 0 AF XY: 0.0733 AC XY: 63 AN XY: 860

Gnomad4 AFR exome AF: 0.350

Gnomad4 AMR exome AF: 0.00

Gnomad4 ASJ exome AF: 0.417

Gnomad4 EAS exome AF: 0.219

Gnomad4 SAS exome AF: 0.0909

Gnomad4 FIN exome AF: 0.00

Gnomad4 NFE exome AF: 0.0481

Gnomad4 OTH exome AF: 0.160

GnomAD4 genome AF: 0.207 AC: 31492 AN: 152038 Hom.: 5239 Cov.: 32 AF XY: 0.207 AC XY: 15392 AN XY: 74334

Gnomad4 AFR AF: 0.442

Gnomad4 AMR AF: 0.154

Gnomad4 ASJ AF: 0.164

Gnomad4 EAS AF: 0.434

Gnomad4 SAS AF: 0.210

Gnomad4 FIN AF: 0.0819

Gnomad4 NFE AF: 0.0823

Gnomad4 OTH AF: 0.212

Alfa AF: 0.0366 Hom.: 48

Bravo AF: 0.225

Asia WGS AF: 0.322 AC: 1122 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.86
CADD	Benign	5.4
DANN	Benign	0.37

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: rs11748158; hg19: chr5-150226345;