5-150848671-T-G

Variant names:

• chr5-150848671-T-G
• rs72553869
• NM_001145805.2:c.*2T>G

Variant summary

Our verdict is Likely benign. The variant received -2 ACMG points: 2P and 4B. PM2 BP4_Strong

The NM_001145805.2(IRGM):​c.*2T>G variant causes a 3 prime UTR change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.000000737 in 1,356,766 control chromosomes in the GnomAD database, with no homozygous occurrence. 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: not found (cov: 32)
  • Exomes 𝑓: 7.4e-7 (0 hom.)
• Consequence: IRGM NM_001145805.2 3_prime_UTR
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -1.11
• 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 -2 ACMG points.

• PM2: Very rare variant in population databases, with high coverage
• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.78).

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
IRGM	NM_001145805.2	c.*2T>G		3_prime_UTR_variant	Exon 2 of 2	ENST00000522154.2	NP_001139277.1
IRGM	NM_001346557.2	c.531+17T>G		intron_variant	Intron 2 of 3		NP_001333486.1
IRGM	NR_170598.1	n.1646+17T>G		intron_variant	Intron 2 of 4

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
IRGM	ENST00000522154.2	c.*2T>G		3_prime_UTR_variant	Exon 2 of 2	1	NM_001145805.2	ENSP00000428220.1
IRGM	ENST00000520549.1	n.156+17T>G		intron_variant	Intron 1 of 3	1		ENSP00000429819.1

Frequencies

GnomAD3 genomes Cov.: 32

GnomAD2 exomes AF: 0.00000791 AC: 1 AN: 126436 AF XY: 0.0000150

Gnomad AFR exome AF: 0.00

Gnomad AMR exome AF: 0.0000503

Gnomad ASJ exome AF: 0.00

Gnomad EAS exome AF: 0.00

Gnomad FIN exome AF: 0.00

Gnomad NFE exome AF: 0.00

Gnomad OTH exome AF: 0.00

GnomAD4 exome AF: 7.37e-7 AC: 1 AN: 1356766 Hom.: 0 Cov.: 27 AF XY: 0.00000150 AC XY: 1 AN XY: 665100

African (AFR) AF: 0.00 AC: 0 AN: 30166

American (AMR) AF: 0.0000325 AC: 1 AN: 30792

Ashkenazi Jewish (ASJ) AF: 0.00 AC: 0 AN: 22984

East Asian (EAS) AF: 0.00 AC: 0 AN: 35324

South Asian (SAS) AF: 0.00 AC: 0 AN: 74310

European-Finnish (FIN) AF: 0.00 AC: 0 AN: 48190

Middle Eastern (MID) AF: 0.00 AC: 0 AN: 5486

European-Non Finnish (NFE) AF: 0.00 AC: 0 AN: 1053456

Other (OTH) AF: 0.00 AC: 0 AN: 56058

GnomAD4 genome Cov.: 32

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.78
CADD	Benign	1.4
DANN	Benign	0.61
PhyloP100		-1.1

Splicing

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

Other links and lift over

dbSNP: rs72553869; hg19: chr5-150228233;