5-150846730-C-T

Variant names:

• chr5-150846730-C-T
• rs11748151
• NM_001145805.2:c.-906C>T

Variant summary

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

The NM_001145805.2(IRGM):​c.-906C>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 0.205 in 152,196 control chromosomes in the GnomAD database, including 5,199 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 (5196 hom., cov: 32)
  • Exomes 𝑓: 0.051 (3 hom.)
• Consequence: IRGM NM_001145805.2 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=-0.9).
• BA1: GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.435 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
IRGM	NM_001145805.2	c.-906C>T		5_prime_UTR_premature_start_codon_gain_variant	Exon 1 of 2	ENST00000522154.2	NP_001139277.1
IRGM	NM_001145805.2	c.-906C>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.-906C>T		5_prime_UTR_premature_start_codon_gain_variant	Exon 1 of 2	1	NM_001145805.2	ENSP00000428220.1
IRGM	ENST00000522154	c.-906C>T		5_prime_UTR_variant	Exon 1 of 2	1	NM_001145805.2	ENSP00000428220.1
IRGM	ENST00000609660.1	n.-73C>T		upstream_gene_variant		6

Frequencies

GnomAD3 genomes AF: 0.205 AC: 31046 AN: 151508 Hom.: 5182 Cov.: 32

Gnomad AFR AF: 0.440

Gnomad AMI AF: 0.0340

Gnomad AMR AF: 0.153

Gnomad ASJ AF: 0.163

Gnomad EAS AF: 0.427

Gnomad SAS AF: 0.208

Gnomad FIN AF: 0.0808

Gnomad MID AF: 0.197

Gnomad NFE AF: 0.0810

Gnomad OTH AF: 0.209

GnomAD4 exome AF: 0.0509 AC: 29 AN: 570 Hom.: 3 Cov.: 0 AF XY: 0.0483 AC XY: 20 AN XY: 414

Gnomad4 AFR exome AF: 0.333

Gnomad4 AMR exome AF: 0.00

Gnomad4 ASJ exome AF: 0.00

Gnomad4 EAS exome AF: 0.227

Gnomad4 SAS exome AF: 0.100

Gnomad4 FIN exome AF: 0.00

Gnomad4 NFE exome AF: 0.0350

Gnomad4 OTH exome AF: 0.0909

GnomAD4 genome AF: 0.205 AC: 31098 AN: 151626 Hom.: 5196 Cov.: 32 AF XY: 0.205 AC XY: 15201 AN XY: 74128

Gnomad4 AFR AF: 0.440

Gnomad4 AMR AF: 0.153

Gnomad4 ASJ AF: 0.163

Gnomad4 EAS AF: 0.428

Gnomad4 SAS AF: 0.207

Gnomad4 FIN AF: 0.0808

Gnomad4 NFE AF: 0.0810

Gnomad4 OTH AF: 0.210

Alfa AF: 0.133 Hom.: 326

Bravo AF: 0.224

Asia WGS AF: 0.321 AC: 1117 AN: 3476

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.90
CADD	Benign	3.8
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: rs11748151; hg19: chr5-150226292;