rs1000113

Variant names:

• chr5-150860514-C-T
• rs1000113
• ENST00000520549.1:n.156+11860C>T

Variant summary

Our verdict is Benign. The variant received -12 ACMG points: 0P and 12B. BP4_Strong BA1

The ENST00000520549.1(IRGM):​n.156+11860C>T variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.137 in 152,106 control chromosomes in the GnomAD database, including 1,904 homozygotes. 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: 𝑓 0.14 (1904 hom., cov: 32)
• Consequence: IRGM ENST00000520549.1 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -1.18
• Publications: 64 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: Benign. The variant received -12 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.91).
• BA1: GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.385 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
IRGM	NM_001346557.2	c.531+11860C>T		intron_variant	Intron 2 of 3		NP_001333486.1
IRGM	NR_170598.1	n.1646+11860C>T		intron_variant	Intron 2 of 4

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
IRGM	ENST00000520549.1	n.156+11860C>T		intron_variant	Intron 1 of 3	1		ENSP00000429819.1

Frequencies

GnomAD3 genomes AF: 0.137 AC: 20787 AN: 151988 Hom.: 1905 Cov.: 32

Gnomad AFR AF: 0.221

Gnomad AMI AF: 0.0296

Gnomad AMR AF: 0.124

Gnomad ASJ AF: 0.161

Gnomad EAS AF: 0.399

Gnomad SAS AF: 0.131

Gnomad FIN AF: 0.0812

Gnomad MID AF: 0.199

Gnomad NFE AF: 0.0770

Gnomad OTH AF: 0.155

We have no GnomAD4 exomes data on this position. Probably position not covered by the project.

GnomAD4 genome AF: 0.137 AC: 20793 AN: 152106 Hom.: 1904 Cov.: 32 AF XY: 0.138 AC XY: 10245 AN XY: 74366

African (AFR) AF: 0.221 AC: 9148 AN: 41448

American (AMR) AF: 0.123 AC: 1884 AN: 15276

Ashkenazi Jewish (ASJ) AF: 0.161 AC: 559 AN: 3468

East Asian (EAS) AF: 0.400 AC: 2064 AN: 5164

South Asian (SAS) AF: 0.130 AC: 626 AN: 4816

European-Finnish (FIN) AF: 0.0812 AC: 861 AN: 10602

Middle Eastern (MID) AF: 0.204 AC: 60 AN: 294

European-Non Finnish (NFE) AF: 0.0771 AC: 5241 AN: 68014

Other (OTH) AF: 0.153 AC: 323 AN: 2112

Alfa AF: 0.107 Hom.: 4738

Bravo AF: 0.147

Asia WGS AF: 0.224 AC: 780 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.91
CADD	Benign	1.3
DANN	Benign	0.44
PhyloP100		-1.2

Splicing

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

Other links and lift over

dbSNP: rs1000113; hg19: chr5-150240076;