rs72553870

Variant names:

• chr5-150848775-T-C
• rs72553870
• ENST00000520549.1:n.156+121T>C

Variant summary

Our verdict is Likely benign. The variant received -4 ACMG points: 0P and 4B. BP4_Strong

The ENST00000520549.1(IRGM):​n.156+121T>C variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.000404 in 792,484 control chromosomes in the GnomAD database, including 1 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 0.0014 (1 hom., cov: 32)
  • Exomes 𝑓: 0.00016 (0 hom.)
• Consequence: IRGM ENST00000520549.1 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 0.447
• Publications: 0 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: Likely_benign. The variant received -4 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.95).

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
IRGM	NM_001346557.2	c.531+121T>C		intron_variant	Intron 2 of 3		NP_001333486.1
IRGM	NR_170598.1	n.1646+121T>C		intron_variant	Intron 2 of 4
IRGM	NM_001145805.2	c.*106T>C		downstream_gene_variant		ENST00000522154.2	NP_001139277.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
IRGM	ENST00000520549.1	n.156+121T>C		intron_variant	Intron 1 of 3	1		ENSP00000429819.1
IRGM	ENST00000522154.2	c.*106T>C		downstream_gene_variant		1	NM_001145805.2	ENSP00000428220.1

Frequencies

GnomAD3 genomes AF: 0.00143 AC: 218 AN: 152134 Hom.: 1 Cov.: 32

Gnomad AFR AF: 0.00422

Gnomad AMI AF: 0.00

Gnomad AMR AF: 0.00236

Gnomad ASJ AF: 0.00

Gnomad EAS AF: 0.00

Gnomad SAS AF: 0.00

Gnomad FIN AF: 0.00

Gnomad MID AF: 0.00

Gnomad NFE AF: 0.00

Gnomad OTH AF: 0.00334

GnomAD4 exome AF: 0.000159 AC: 102 AN: 640232 Hom.: 0 AF XY: 0.000119 AC XY: 39 AN XY: 326874

African (AFR) AF: 0.00426 AC: 67 AN: 15742

American (AMR) AF: 0.000889 AC: 17 AN: 19122

Ashkenazi Jewish (ASJ) AF: 0.00 AC: 0 AN: 14874

East Asian (EAS) AF: 0.00 AC: 0 AN: 31974

South Asian (SAS) AF: 0.00 AC: 0 AN: 48430

European-Finnish (FIN) AF: 0.00 AC: 0 AN: 43778

Middle Eastern (MID) AF: 0.00 AC: 0 AN: 2378

European-Non Finnish (NFE) AF: 0.0000116 AC: 5 AN: 432026

Other (OTH) AF: 0.000407 AC: 13 AN: 31908

GnomAD4 genome AF: 0.00143 AC: 218 AN: 152252 Hom.: 1 Cov.: 32 AF XY: 0.00118 AC XY: 88 AN XY: 74454

African (AFR) AF: 0.00421 AC: 175 AN: 41552

American (AMR) AF: 0.00235 AC: 36 AN: 15290

Ashkenazi Jewish (ASJ) AF: 0.00 AC: 0 AN: 3468

East Asian (EAS) AF: 0.00 AC: 0 AN: 5174

South Asian (SAS) AF: 0.00 AC: 0 AN: 4814

European-Finnish (FIN) AF: 0.00 AC: 0 AN: 10616

Middle Eastern (MID) AF: 0.00 AC: 0 AN: 294

European-Non Finnish (NFE) AF: 0.00 AC: 0 AN: 68016

Other (OTH) AF: 0.00331 AC: 7 AN: 2116

Alfa AF: 0.000971 Hom.: 1

Bravo AF: 0.00198

Asia WGS AF: 0.000289 AC: 1 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.95
CADD	Benign	6.3
DANN	Benign	0.52
PhyloP100		0.45

Splicing

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

Other links and lift over

dbSNP: rs72553870; hg19: chr5-150228337;