rs7705542

Positions:

• chr5-150848756-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+102G>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 0.131 in 936,924 control chromosomes in the GnomAD database, including 13,890 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 (5239 hom., cov: 32)
  • Exomes 𝑓: 0.12 (8651 hom.)
• Consequence: IRGM ENST00000520549.1 intron, NMD_transcript
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -1.28

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=-0.89).
• BA1: GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.437 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
IRGM	NM_001346557.2	c.531+102G>A		intron_variant			NP_001333486.1
IRGM	NR_170598.1	n.1646+102G>A		intron_variant, non_coding_transcript_variant

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
IRGM	ENST00000520549.1	c.158+102G>A		intron_variant, NMD_transcript_variant		1		ENSP00000429819

Frequencies

GnomAD3 genomes AF: 0.207 AC: 31421 AN: 151888 Hom.: 5225 Cov.: 32

Gnomad AFR AF: 0.443

Gnomad AMI AF: 0.0352

Gnomad AMR AF: 0.154

Gnomad ASJ AF: 0.164

Gnomad EAS AF: 0.433

Gnomad SAS AF: 0.211

Gnomad FIN AF: 0.0822

Gnomad MID AF: 0.206

Gnomad NFE AF: 0.0818

Gnomad OTH AF: 0.211

GnomAD4 exome AF: 0.116 AC: 91214 AN: 784918 Hom.: 8651 AF XY: 0.118 AC XY: 46839 AN XY: 395388

Gnomad4 AFR exome AF: 0.446

Gnomad4 AMR exome AF: 0.148

Gnomad4 ASJ exome AF: 0.171

Gnomad4 EAS exome AF: 0.386

Gnomad4 SAS exome AF: 0.201

Gnomad4 FIN exome AF: 0.0831

Gnomad4 NFE exome AF: 0.0789

Gnomad4 OTH exome AF: 0.154

GnomAD4 genome AF: 0.207 AC: 31474 AN: 152006 Hom.: 5239 Cov.: 32 AF XY: 0.207 AC XY: 15387 AN XY: 74310

Gnomad4 AFR AF: 0.443

Gnomad4 AMR AF: 0.154

Gnomad4 ASJ AF: 0.164

Gnomad4 EAS AF: 0.434

Gnomad4 SAS AF: 0.210

Gnomad4 FIN AF: 0.0822

Gnomad4 NFE AF: 0.0819

Gnomad4 OTH AF: 0.213

Alfa AF: 0.182 Hom.: 631

Bravo AF: 0.224

Asia WGS AF: 0.323 AC: 1123 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.89
CADD	Benign	1.4
DANN	Benign	0.80

Splicing

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

Publications

LitVar

Other links and lift over

dbSNP: rs7705542; hg19: chr5-150228318;