5-150848438-G-T

Variant names:

• chr5-150848438-G-T
• NM_001145805.2:c.315G>T
• IRGM p.Leu105Leu

Variant summary

Our verdict is Likely benign. The variant received -3 ACMG points: 2P and 5B. PM2 BP4_Strong BP7

The NM_001145805.2(IRGM):​c.315G>T​(p.Leu105Leu) variant causes a synonymous 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. Synonymous variant affecting the same amino acid position (i.e. L105L) has been classified as Benign.

• Frequency: Genomes: not found (cov: 32)
• Consequence: IRGM NM_001145805.2 synonymous
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.722
• 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 -3 ACMG points.

• PM2: Very rare variant in population databases, with high coverage
• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.92).
• BP7: Synonymous conserved (PhyloP=-0.722 with no splicing effect.

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_001145805.2. You can select a different transcript below to see updated ACMG assignments.

RefSeq Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	IRGM	NM_001145805.2	MANE Select	c.315G>T	p.Leu105Leu	synonymous	Exon 2 of 2	NP_001139277.1	A1A4Y4-1
	IRGM	NM_001346557.2		c.315G>T	p.Leu105Leu	synonymous	Exon 2 of 4	NP_001333486.1	A1A4Y4-2
	IRGM	NR_170598.1		n.1430G>T		non_coding_transcript_exon	Exon 2 of 5

Ensembl Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	IRGM	ENST00000522154.2	TSL:1 MANE Select	c.315G>T	p.Leu105Leu	synonymous	Exon 2 of 2	ENSP00000428220.1	A1A4Y4-1
	IRGM	ENST00000951736.1		c.315G>T	p.Leu105Leu	synonymous	Exon 2 of 2	ENSP00000621795.1
	IRGM	ENST00000520549.1	TSL:1	n.-61G>T		upstream_gene	N/A	ENSP00000429819.1	A0A9H4B933

Frequencies

GnomAD3 genomes Cov.: 32

GnomAD4 exome Cov.: 32

GnomAD4 genome Cov.: 32

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.92
CADD	Benign	0.29
DANN	Benign	0.35
PhyloP100		-0.72

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

MaxEntScan Visualizer can be used to analyze the impact of this mutation on the neighboring sequence.

Other links and lift over

hg19: chr5-150228000;