5-150847558-G-C

Position:

• chr5-150847558-G-C

Variant summary

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

The NM_001145805.2(IRGM):​c.-415-151G>C variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0547 in 153,366 control chromosomes in the GnomAD database, including 784 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 0.055 (784 hom., cov: 32)
  • Exomes 𝑓: 0.0026 (0 hom.)
• Consequence: IRGM NM_001145805.2 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 1.28

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=-0.89).
• BA1: GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.188 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
IRGM	NM_001145805.2	c.-415-151G>C		intron_variant		ENST00000522154.2	NP_001139277.1
IRGM	NM_001346557.2	c.-415-151G>C		intron_variant			NP_001333486.1
IRGM	NR_170598.1	n.701-151G>C		intron_variant

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
IRGM	ENST00000522154.2	c.-415-151G>C		intron_variant		1	NM_001145805.2	ENSP00000428220.1

Frequencies

GnomAD3 genomes AF: 0.0551 AC: 8375 AN: 152084 Hom.: 781 Cov.: 32

Gnomad AFR AF: 0.192

Gnomad AMI AF: 0.00

Gnomad AMR AF: 0.0212

Gnomad ASJ AF: 0.00

Gnomad EAS AF: 0.00

Gnomad SAS AF: 0.00145

Gnomad FIN AF: 0.00

Gnomad MID AF: 0.0158

Gnomad NFE AF: 0.000617

Gnomad OTH AF: 0.0354

GnomAD4 exome AF: 0.00258 AC: 3 AN: 1164 Hom.: 0 Cov.: 0 AF XY: 0.00163 AC XY: 1 AN XY: 612

Gnomad4 AFR exome AF: 0.00

Gnomad4 AMR exome AF: 0.0125

Gnomad4 ASJ exome AF: 0.00

Gnomad4 EAS exome AF: 0.00725

Gnomad4 SAS exome AF: 0.00

Gnomad4 FIN exome AF: 0.00

Gnomad4 NFE exome AF: 0.00

Gnomad4 OTH exome AF: 0.00

GnomAD4 genome AF: 0.0551 AC: 8391 AN: 152202 Hom.: 784 Cov.: 32 AF XY: 0.0534 AC XY: 3973 AN XY: 74446

Gnomad4 AFR AF: 0.192

Gnomad4 AMR AF: 0.0212

Gnomad4 ASJ AF: 0.00

Gnomad4 EAS AF: 0.00

Gnomad4 SAS AF: 0.00124

Gnomad4 FIN AF: 0.00

Gnomad4 NFE AF: 0.000617

Gnomad4 OTH AF: 0.0351

Alfa AF: 0.0438 Hom.: 61

Bravo AF: 0.0633

Asia WGS AF: 0.0130 AC: 47 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.89
CADD	Benign	3.0
DANN	Benign	0.45

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: rs17111379; hg19: chr5-150227120;