rs11747270

Positions:

• chr5-150879305-A-G

Variant summary

Our verdict is Benign. Variant got -12 ACMG points: 0P and 12B. BP4_Strong BA1

The ENST00000520549.1(IRGM):​c.*79-280A>G variant causes a intron, NMD transcript 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, NMD_transcript
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.792

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

Verdict is Benign. Variant got -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/exons	MANE	Protein	UniProt
IRGM	NM_001346557.2	c.532-280A>G		intron_variant			NP_001333486.1
IRGM	NR_170598.1	n.1782-280A>G		intron_variant, non_coding_transcript_variant

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
IRGM	ENST00000520549.1	c.*79-280A>G		intron_variant, NMD_transcript_variant		1		ENSP00000429819

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

Gnomad4 AFR AF: 0.450

Gnomad4 AMR AF: 0.155

Gnomad4 ASJ AF: 0.164

Gnomad4 EAS AF: 0.433

Gnomad4 SAS AF: 0.210

Gnomad4 FIN AF: 0.0818

Gnomad4 NFE AF: 0.0814

Gnomad4 OTH AF: 0.216

Alfa AF: 0.121 Hom.: 2705

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

Splicing

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

Publications

LitVar

Other links and lift over

dbSNP: rs11747270; hg19: chr5-150258867;