ENST00000520549.1:n.156+90A>T

Variant names:

• chr5-150848742-G-T
• ENST00000520549.1:n.156+88G>T

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+88G>T variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant was absent in control chromosomes in GnomAD project. 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: 0.0 (0 hom.)
  • Failed GnomAD Quality Control
• Consequence: IRGM ENST00000520549.1 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 1.15
• 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=-0.89).

Variant Effect in Transcripts

ACMG analysis was done for transcript: ENST00000520549.1. You can select a different transcript below to see updated ACMG assignments.

RefSeq Transcripts

Selected	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	IRGM	NM_001346557.2		c.531+88G>T		intron	N/A	NP_001333486.1
	IRGM	NR_170598.1		n.1646+88G>T		intron	N/A
	IRGM	NM_001145805.2	MANE Select	c.*73G>T		downstream_gene	N/A	NP_001139277.1

Ensembl Transcripts

Selected	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	IRGM	ENST00000520549.1	TSL:1	n.156+88G>T		intron	N/A	ENSP00000429819.1
	IRGM	ENST00000522154.2	TSL:1 MANE Select	c.*73G>T		downstream_gene	N/A	ENSP00000428220.1
	IRGM	ENST00000951736.1		c.*73G>T		downstream_gene	N/A	ENSP00000621795.1

Frequencies

GnomAD3 genomes Cov.: 32

GnomAD4 exome Data not reliable, filtered out with message: AC0 AF: 0.00 AC: 0 AN: 923474 Hom.: 0 AF XY: 0.00 AC XY: 0 AN XY: 461378

African (AFR) AF: 0.00 AC: 0 AN: 21508

American (AMR) AF: 0.00 AC: 0 AN: 22930

Ashkenazi Jewish (ASJ) AF: 0.00 AC: 0 AN: 17252

East Asian (EAS) AF: 0.00 AC: 0 AN: 33430

South Asian (SAS) AF: 0.00 AC: 0 AN: 56278

European-Finnish (FIN) AF: 0.00 AC: 0 AN: 44694

Middle Eastern (MID) AF: 0.00 AC: 0 AN: 3318

European-Non Finnish (NFE) AF: 0.00 AC: 0 AN: 682562

Other (OTH) AF: 0.00 AC: 0 AN: 41502

GnomAD4 genome Cov.: 32

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.89
CADD	Benign	5.6
DANN	Benign	0.67
PhyloP100		1.2

Splicing

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

Other links and lift over

hg19: chr5-150228304;