rs1231285208

Variant names:

• chr5-150848748-C-A
• rs1231285208
• ENST00000520549.1:n.156+94C>A

Your query was ambiguous. Multiple possible variants found:

• chr5-150848748-C-A
• chr5-150848748-C-T

Variant summary

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

The NM_001346557.2(IRGM):​c.531+94C>A variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00000471 in 848,762 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: 0.0000047 (0 hom.)
• Consequence: IRGM NM_001346557.2 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.450
• 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=-0.86).

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_001346557.2. 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+94C>A		intron	N/A	NP_001333486.1
	IRGM	NR_170598.1		n.1646+94C>A		intron	N/A
	IRGM	NM_001145805.2	MANE Select	c.*79C>A		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+94C>A		intron	N/A	ENSP00000429819.1
	IRGM	ENST00000522154.2	TSL:1 MANE Select	c.*79C>A		downstream_gene	N/A	ENSP00000428220.1
	IRGM	ENST00000951736.1		c.*79C>A		downstream_gene	N/A	ENSP00000621795.1

Frequencies

GnomAD3 genomes Cov.: 32

GnomAD4 exome AF: 0.00000471 AC: 4 AN: 848762 Hom.: 0 AF XY: 0.00000704 AC XY: 3 AN XY: 425902

⚠️ 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: 20142

American (AMR) AF: 0.00 AC: 0 AN: 22024

Ashkenazi Jewish (ASJ) AF: 0.00 AC: 0 AN: 16622

East Asian (EAS) AF: 0.00 AC: 0 AN: 33110

South Asian (SAS) AF: 0.00 AC: 0 AN: 54350

European-Finnish (FIN) AF: 0.00 AC: 0 AN: 44516

Middle Eastern (MID) AF: 0.00 AC: 0 AN: 3040

European-Non Finnish (NFE) AF: 0.00000649 AC: 4 AN: 615924

Other (OTH) AF: 0.00 AC: 0 AN: 39034

⚠️ 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	-0.86
CADD	Benign	2.6
DANN	Benign	0.69
PhyloP100		-0.45

Splicing

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

Other links and lift over

dbSNP: rs1231285208; hg19: chr5-150228310;