rs7705542

Variant names:

• chr5-150848756-G-A
• rs7705542
• ENST00000520549.1:n.156+102G>A

Variant summary

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

The ENST00000520549.1(IRGM):​n.156+102G>A variant causes a intron 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
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -1.28
• Publications: 11 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=-0.89).
• BA1: GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.437 is higher than 0.05.

Variant Effect in Transcripts

ACMG analysis was done for transcript: ENST00000520549.1. You can select a different transcript below to see updated ACMG assignments.

RefSeq Transcripts

Selected	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	IRGM	NM_001346557.2		c.531+102G>A		intron	N/A	NP_001333486.1
	IRGM	NR_170598.1		n.1646+102G>A		intron	N/A
	IRGM	NM_001145805.2	MANE Select	c.*87G>A		downstream_gene	N/A	NP_001139277.1

Ensembl Transcripts

Selected	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	IRGM	ENST00000520549.1	TSL:1	n.156+102G>A		intron	N/A	ENSP00000429819.1
	IRGM	ENST00000522154.2	TSL:1 MANE Select	c.*87G>A		downstream_gene	N/A	ENSP00000428220.1

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

African (AFR) AF: 0.446 AC: 8191 AN: 18354

American (AMR) AF: 0.148 AC: 3034 AN: 20532

Ashkenazi Jewish (ASJ) AF: 0.171 AC: 2732 AN: 15932

East Asian (EAS) AF: 0.386 AC: 12615 AN: 32666

South Asian (SAS) AF: 0.201 AC: 10442 AN: 52048

European-Finnish (FIN) AF: 0.0831 AC: 3679 AN: 44272

Middle Eastern (MID) AF: 0.219 AC: 605 AN: 2762

European-Non Finnish (NFE) AF: 0.0789 AC: 44291 AN: 561708

Other (OTH) AF: 0.154 AC: 5625 AN: 36644

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

African (AFR) AF: 0.443 AC: 18326 AN: 41400

American (AMR) AF: 0.154 AC: 2354 AN: 15288

Ashkenazi Jewish (ASJ) AF: 0.164 AC: 567 AN: 3466

East Asian (EAS) AF: 0.434 AC: 2240 AN: 5164

South Asian (SAS) AF: 0.210 AC: 1010 AN: 4812

European-Finnish (FIN) AF: 0.0822 AC: 870 AN: 10588

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

European-Non Finnish (NFE) AF: 0.0819 AC: 5564 AN: 67974

Other (OTH) AF: 0.213 AC: 449 AN: 2110

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 v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.89
CADD	Benign	1.4
DANN	Benign	0.80
PhyloP100		-1.3
Mutation Taster		=100/0	polymorphism (auto)

Splicing

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

Other links and lift over

dbSNP: rs7705542; hg19: chr5-150228318; COSMIC: COSV107544576;