ENST00000520549.1:n.156+111T>C

Variant names:

• chr5-150848763-G-C
• rs1753928745
• ENST00000520549.1:n.156+109G>C

Variant summary

Our verdict is Likely benign. The variant received -2 ACMG points: 2P and 4B. PM2 BP4_Strong

The ENST00000520549.1(IRGM):​n.156+109G>C variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00000541 in 739,084 control chromosomes in the GnomAD database, with no homozygous occurrence. 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: not found (cov: 32)
  • Exomes 𝑓: 0.0000054 (0 hom.)
• Consequence: IRGM ENST00000520549.1 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 0.761
• Publications: 0 publications found

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

Our verdict: Likely_benign. The variant received -2 ACMG points.

• PM2: Very rare variant in population databases, with high coverage
• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.91).

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
IRGM	NM_001346557.2	c.531+109G>C		intron_variant	Intron 2 of 3		NP_001333486.1
IRGM	NR_170598.1	n.1646+109G>C		intron_variant	Intron 2 of 4
IRGM	NM_001145805.2	c.*94G>C		downstream_gene_variant		ENST00000522154.2	NP_001139277.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
IRGM	ENST00000520549.1	n.156+109G>C		intron_variant	Intron 1 of 3	1		ENSP00000429819.1
IRGM	ENST00000522154.2	c.*94G>C		downstream_gene_variant		1	NM_001145805.2	ENSP00000428220.1

Frequencies

GnomAD3 genomes Cov.: 32

GnomAD4 exome AF: 0.00000541 AC: 4 AN: 739084 Hom.: 0 AF XY: 0.00000536 AC XY: 2 AN XY: 373212

African (AFR) AF: 0.00 AC: 0 AN: 17358

American (AMR) AF: 0.00 AC: 0 AN: 19398

Ashkenazi Jewish (ASJ) AF: 0.00 AC: 0 AN: 15458

East Asian (EAS) AF: 0.00 AC: 0 AN: 32402

South Asian (SAS) AF: 0.00 AC: 0 AN: 50272

European-Finnish (FIN) AF: 0.00 AC: 0 AN: 44050

Middle Eastern (MID) AF: 0.00 AC: 0 AN: 2608

European-Non Finnish (NFE) AF: 0.00000766 AC: 4 AN: 522422

Other (OTH) AF: 0.00 AC: 0 AN: 35116

GnomAD4 genome Cov.: 32

Alfa AF: 0.00 Hom.: 0

Bravo AF: 0.00000378

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.91
CADD	Benign	1.4
DANN	Benign	0.69
PhyloP100		0.76

Splicing

Find out detailed SpliceAI scores and Pangolin per-transcript scores at spliceailookup.broadinstitute.org

Other links and lift over

dbSNP: rs1753928745; hg19: chr5-150228325;