rs4958847

Variant names:

• chr5-150860025-G-A
• rs4958847
• ENST00000520549.1:n.156+11371G>A

Variant summary

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

The ENST00000520549.1(IRGM):​n.156+11371G>A variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.249 in 151,964 control chromosomes in the GnomAD database, including 6,791 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 0.25 (6791 hom., cov: 32)
• Consequence: IRGM ENST00000520549.1 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.786
• Publications: 88 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=-0.93).
• BA1: GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.596 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
IRGM	NM_001346557.2	c.531+11371G>A		intron_variant	Intron 2 of 3		NP_001333486.1
IRGM	NR_170598.1	n.1646+11371G>A		intron_variant	Intron 2 of 4

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
IRGM	ENST00000520549.1	n.156+11371G>A		intron_variant	Intron 1 of 3	1		ENSP00000429819.1

Frequencies

GnomAD3 genomes AF: 0.249 AC: 37803 AN: 151846 Hom.: 6772 Cov.: 32

Gnomad AFR AF: 0.468

Gnomad AMI AF: 0.159

Gnomad AMR AF: 0.186

Gnomad ASJ AF: 0.200

Gnomad EAS AF: 0.614

Gnomad SAS AF: 0.274

Gnomad FIN AF: 0.114

Gnomad MID AF: 0.315

Gnomad NFE AF: 0.124

Gnomad OTH AF: 0.251

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

GnomAD4 genome AF: 0.249 AC: 37862 AN: 151964 Hom.: 6791 Cov.: 32 AF XY: 0.250 AC XY: 18601 AN XY: 74286

African (AFR) AF: 0.468 AC: 19411 AN: 41436

American (AMR) AF: 0.186 AC: 2841 AN: 15270

Ashkenazi Jewish (ASJ) AF: 0.200 AC: 694 AN: 3464

East Asian (EAS) AF: 0.614 AC: 3171 AN: 5164

South Asian (SAS) AF: 0.273 AC: 1312 AN: 4808

European-Finnish (FIN) AF: 0.114 AC: 1206 AN: 10568

Middle Eastern (MID) AF: 0.315 AC: 92 AN: 292

European-Non Finnish (NFE) AF: 0.125 AC: 8460 AN: 67946

Other (OTH) AF: 0.252 AC: 530 AN: 2106

Alfa AF: 0.174 Hom.: 1852

Bravo AF: 0.267

Asia WGS AF: 0.415 AC: 1443 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.93
CADD	Benign	0.66
DANN	Benign	0.63
PhyloP100		-0.79

Splicing

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

Other links and lift over

dbSNP: rs4958847; hg19: chr5-150239587;