rs4958847

chr5-150860025-G-A

Variant summary

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

The ENST00000520549.1(IRGM):c.158+11371G>A variant causes a intron, NMD transcript change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.249 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, NMD_transcript
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.786

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=-0.93).
• 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/exons	MANE	UniProt
IRGM	NM_001346557.2	c.531+11371G>A		intron_variant
IRGM	NR_170598.1	n.1646+11371G>A		intron_variant, non_coding_transcript_variant

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
IRGM	ENST00000520549.1	c.158+11371G>A		intron_variant, NMD_transcript_variant		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

Gnomad4 AFR AF: 0.468

Gnomad4 AMR AF: 0.186

Gnomad4 ASJ AF: 0.200

Gnomad4 EAS AF: 0.614

Gnomad4 SAS AF: 0.273

Gnomad4 FIN AF: 0.114

Gnomad4 NFE AF: 0.125

Gnomad4 OTH AF: 0.252

Alfa AF: 0.173 Hom.: 1677

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

Splicing

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

Publications

LitVar

Other links and lift over

dbSNP: rs4958847; hg19: chr5-150239587;