rs1428554

Positions:

• chr5-150878054-A-G
• chr5-150878054-A-T

Variant summary

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

The NM_001346557.2(IRGM):​c.532-1531A>G variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.161 in 460,854 control chromosomes in the GnomAD database, including 9,594 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 (5206 hom., cov: 32)
  • Exomes 𝑓: 0.14 (4388 hom.)
• Consequence: IRGM NM_001346557.2 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 3.44

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=-0.65).
• BA1: GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.439 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
IRGM	NM_001346557.2	c.532-1531A>G		intron_variant			NP_001333486.1
IRGM	NR_170598.1	n.1721A>G		non_coding_transcript_exon_variant	3/5

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
IRGM	ENST00000520549.1	n.*18A>G		non_coding_transcript_exon_variant	2/4	1		ENSP00000429819.1
IRGM	ENST00000520549.1	n.*18A>G		3_prime_UTR_variant	2/4	1		ENSP00000429819.1

Frequencies

GnomAD3 genomes AF: 0.207 AC: 31384 AN: 151880 Hom.: 5192 Cov.: 32

Gnomad AFR AF: 0.444

Gnomad AMI AF: 0.0351

Gnomad AMR AF: 0.154

Gnomad ASJ AF: 0.163

Gnomad EAS AF: 0.427

Gnomad SAS AF: 0.209

Gnomad FIN AF: 0.0816

Gnomad MID AF: 0.206

Gnomad NFE AF: 0.0815

Gnomad OTH AF: 0.211

GnomAD3 exomes AF: 0.164 AC: 23737 AN: 144958 Hom.: 2956 AF XY: 0.162 AC XY: 12670 AN XY: 78246

Gnomad AFR exome AF: 0.448

Gnomad AMR exome AF: 0.142

Gnomad ASJ exome AF: 0.173

Gnomad EAS exome AF: 0.440

Gnomad SAS exome AF: 0.199

Gnomad FIN exome AF: 0.0866

Gnomad NFE exome AF: 0.0847

Gnomad OTH exome AF: 0.160

GnomAD4 exome AF: 0.138 AC: 42650 AN: 308856 Hom.: 4388 Cov.: 0 AF XY: 0.141 AC XY: 24877 AN XY: 175914

Gnomad4 AFR exome AF: 0.454

Gnomad4 AMR exome AF: 0.142

Gnomad4 ASJ exome AF: 0.174

Gnomad4 EAS exome AF: 0.431

Gnomad4 SAS exome AF: 0.194

Gnomad4 FIN exome AF: 0.0817

Gnomad4 NFE exome AF: 0.0815

Gnomad4 OTH exome AF: 0.158

GnomAD4 genome AF: 0.207 AC: 31438 AN: 151998 Hom.: 5206 Cov.: 32 AF XY: 0.206 AC XY: 15330 AN XY: 74324

Gnomad4 AFR AF: 0.444

Gnomad4 AMR AF: 0.154

Gnomad4 ASJ AF: 0.163

Gnomad4 EAS AF: 0.427

Gnomad4 SAS AF: 0.208

Gnomad4 FIN AF: 0.0816

Gnomad4 NFE AF: 0.0815

Gnomad4 OTH AF: 0.213

Alfa AF: 0.121 Hom.: 1735

Bravo AF: 0.226

Asia WGS AF: 0.320 AC: 1114 AN: 3476

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.65
CADD	Benign	14
DANN	Benign	0.25

Splicing

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

Publications

LitVar

Other links and lift over

dbSNP: rs1428554; hg19: chr5-150257616;