rs7714584

Variant names:

• chr5-150890858-A-G
• rs7714584
• ENST00000520549.1:n.*141-9731A>G

Variant summary

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

The ENST00000520549.1(IRGM):​n.*141-9731A>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 151,920 control chromosomes in the GnomAD database, including 5,365 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 (5365 hom., cov: 32)
• Consequence: IRGM ENST00000520549.1 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 0.316
• Publications: 47 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=-0.76).
• 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.594-9731A>G		intron_variant	Intron 3 of 3		NP_001333486.1
IRGM	NR_170598.1	n.1844-9731A>G		intron_variant	Intron 4 of 4

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
IRGM	ENST00000520549.1	n.*141-9731A>G		intron_variant	Intron 3 of 3	1		ENSP00000429819.1

Frequencies

GnomAD3 genomes AF: 0.209 AC: 31711 AN: 151804 Hom.: 5350 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: 0.433

Gnomad SAS AF: 0.211

Gnomad FIN AF: 0.0819

Gnomad MID AF: 0.204

Gnomad NFE AF: 0.0815

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: 31771 AN: 151920 Hom.: 5365 Cov.: 32 AF XY: 0.209 AC XY: 15508 AN XY: 74278

African (AFR) AF: 0.450 AC: 18641 AN: 41414

American (AMR) AF: 0.155 AC: 2359 AN: 15234

Ashkenazi Jewish (ASJ) AF: 0.164 AC: 569 AN: 3472

East Asian (EAS) AF: 0.434 AC: 2241 AN: 5166

South Asian (SAS) AF: 0.210 AC: 1012 AN: 4824

European-Finnish (FIN) AF: 0.0819 AC: 868 AN: 10598

Middle Eastern (MID) AF: 0.209 AC: 61 AN: 292

European-Non Finnish (NFE) AF: 0.0815 AC: 5534 AN: 67906

Other (OTH) AF: 0.216 AC: 454 AN: 2102

Alfa AF: 0.122 Hom.: 8504

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	-0.76
CADD	Benign	7.5
DANN	Benign	0.90
PhyloP100		0.32

Splicing

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

Other links and lift over

dbSNP: rs7714584; hg19: chr5-150270420;