ENST00000520549.1:n.156+94C>T

Variant names:

• chr5-150848746-C-T
• rs1753928304
• ENST00000520549.1:n.156+92C>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+92C>T variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00000228 in 878,012 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: 0.0000023 (0 hom.)
• Consequence: IRGM ENST00000520549.1 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.936
• 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=-0.83).

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+92C>T		intron	N/A	NP_001333486.1
	IRGM	NR_170598.1		n.1646+92C>T		intron	N/A
	IRGM	NM_001145805.2	MANE Select	c.*77C>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+92C>T		intron	N/A	ENSP00000429819.1
	IRGM	ENST00000522154.2	TSL:1 MANE Select	c.*77C>T		downstream_gene	N/A	ENSP00000428220.1
	IRGM	ENST00000951736.1		c.*77C>T		downstream_gene	N/A	ENSP00000621795.1

Frequencies

GnomAD3 genomes Cov.: 32

GnomAD4 exome AF: 0.00000228 AC: 2 AN: 878012 Hom.: 0 AF XY: 0.00000227 AC XY: 1 AN XY: 439824

⚠️ The allele balance in gnomAD version 4 Exomes is significantly skewed from the expected value of 0.5.

African (AFR) AF: 0.00 AC: 0 AN: 20548

American (AMR) AF: 0.00 AC: 0 AN: 22536

Ashkenazi Jewish (ASJ) AF: 0.00 AC: 0 AN: 16906

East Asian (EAS) AF: 0.00 AC: 0 AN: 33216

South Asian (SAS) AF: 0.00 AC: 0 AN: 55040

European-Finnish (FIN) AF: 0.00 AC: 0 AN: 44616

Middle Eastern (MID) AF: 0.00 AC: 0 AN: 3128

European-Non Finnish (NFE) AF: 0.00000311 AC: 2 AN: 642076

Other (OTH) AF: 0.00 AC: 0 AN: 39946

⚠️ The allele balance in gnomAD4 Exomes is highly skewed from 0.5 (p-value = 0), which strongly suggests a high chance of mosaicism in these individuals.

GnomAD4 genome Cov.: 32

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.83
CADD	Benign	3.3
DANN	Benign	0.76
PhyloP100		-0.94

Splicing

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

Other links and lift over

dbSNP: rs1753928304; hg19: chr5-150228308;