5-150848053-G-T

Variant names:

• chr5-150848053-G-T
• rs9637870
• NM_001145805.2:c.-71G>T

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.-71G>T variant causes a 5 prime UTR premature start codon gain change involving the alteration of a non-conserved nucleotide. The variant was absent in control chromosomes in GnomAD project. 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: 0.0 (0 hom.)
  • Failed GnomAD Quality Control
• Consequence: IRGM NM_001145805.2 5_prime_UTR_premature_start_codon_gain
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.104
• 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: 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=-1.01).

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_001145805.2. 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_001145805.2	MANE Select	c.-71G>T		5_prime_UTR_premature_start_codon_gain	Exon 2 of 2	NP_001139277.1
	IRGM	NM_001145805.2	MANE Select	c.-71G>T		5_prime_UTR	Exon 2 of 2	NP_001139277.1
	IRGM	NM_001346557.2		c.-71G>T		5_prime_UTR_premature_start_codon_gain	Exon 2 of 4	NP_001333486.1

Ensembl Transcripts

Selected	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	IRGM	ENST00000522154.2	TSL:1 MANE Select	c.-71G>T		5_prime_UTR_premature_start_codon_gain	Exon 2 of 2	ENSP00000428220.1
	IRGM	ENST00000522154.2	TSL:1 MANE Select	c.-71G>T		5_prime_UTR	Exon 2 of 2	ENSP00000428220.1

Frequencies

GnomAD3 genomes Cov.: 32

GnomAD4 exome Data not reliable, filtered out with message: AC0 AF: 0.00 AC: 0 AN: 1080706 Hom.: 0 Cov.: 14 AF XY: 0.00 AC XY: 0 AN XY: 534346

African (AFR) AF: 0.00 AC: 0 AN: 24246

American (AMR) AF: 0.00 AC: 0 AN: 22836

Ashkenazi Jewish (ASJ) AF: 0.00 AC: 0 AN: 18124

East Asian (EAS) AF: 0.00 AC: 0 AN: 34022

South Asian (SAS) AF: 0.00 AC: 0 AN: 59572

European-Finnish (FIN) AF: 0.00 AC: 0 AN: 45512

Middle Eastern (MID) AF: 0.00 AC: 0 AN: 4456

European-Non Finnish (NFE) AF: 0.00 AC: 0 AN: 825462

Other (OTH) AF: 0.00 AC: 0 AN: 46476

GnomAD4 genome Cov.: 32

Alfa AF: 0.00 Hom.: 34

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-1.0
CADD	Benign	0.76
DANN	Benign	0.38
PhyloP100		-0.10

Splicing

Name	Calibrated prediction	Score	Prediction
SpliceAI score (max)		0.020		Details are displayed if max score is > 0.2

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

Other links and lift over

dbSNP: rs9637870; hg19: chr5-150227615;