rs11747270

Variant names:

• chr5-150879305-A-G
• rs11747270
• ENST00000520549.1:n.*79-280A>G

Variant summary

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

The ENST00000520549.1(IRGM):​n.*79-280A>G variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.209 in 152,138 control chromosomes in the GnomAD database, including 5,370 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 0.21 (5370 hom., cov: 32)
• Consequence: IRGM ENST00000520549.1 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.792
• Publications: 70 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=-0.84).
• BA1: GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.445 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
IRGM	NM_001346557.2	c.532-280A>G		intron_variant	Intron 2 of 3		NP_001333486.1
IRGM	NR_170598.1	n.1782-280A>G		intron_variant	Intron 3 of 4

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
IRGM	ENST00000520549.1	n.*79-280A>G		intron_variant	Intron 2 of 3	1		ENSP00000429819.1

Frequencies

GnomAD3 genomes AF: 0.209 AC: 31741 AN: 152020 Hom.: 5354 Cov.: 32

Gnomad AFR AF: 0.450

Gnomad AMI AF: 0.0351

Gnomad AMR AF: 0.155

Gnomad ASJ AF: 0.164

Gnomad EAS AF: 0.432

Gnomad SAS AF: 0.211

Gnomad FIN AF: 0.0818

Gnomad MID AF: 0.206

Gnomad NFE AF: 0.0814

Gnomad OTH AF: 0.214

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

GnomAD4 genome AF: 0.209 AC: 31803 AN: 152138 Hom.: 5370 Cov.: 32 AF XY: 0.209 AC XY: 15516 AN XY: 74386

African (AFR) AF: 0.450 AC: 18662 AN: 41464

American (AMR) AF: 0.155 AC: 2367 AN: 15286

Ashkenazi Jewish (ASJ) AF: 0.164 AC: 568 AN: 3468

East Asian (EAS) AF: 0.433 AC: 2238 AN: 5170

South Asian (SAS) AF: 0.210 AC: 1012 AN: 4826

European-Finnish (FIN) AF: 0.0818 AC: 867 AN: 10600

Middle Eastern (MID) AF: 0.211 AC: 62 AN: 294

European-Non Finnish (NFE) AF: 0.0814 AC: 5539 AN: 68008

Other (OTH) AF: 0.216 AC: 456 AN: 2110

Alfa AF: 0.131 Hom.: 7436

Bravo AF: 0.227

Asia WGS AF: 0.322 AC: 1120 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.84
CADD	Benign	5.1
DANN	Benign	0.90
PhyloP100		-0.79

Splicing

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

Other links and lift over

dbSNP: rs11747270; hg19: chr5-150258867;