5-150846533-A-G

Variant names:

• chr5-150846533-A-G
• rs12654043
• NM_001145805.2:c.-1103A>G

Variant summary

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

The NM_001145805.2(IRGM):​c.-1103A>G variant causes a 5 prime UTR change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.289 in 151,028 control chromosomes in the GnomAD database, including 8,069 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 0.29 (8068 hom., cov: 32)
  • Exomes 𝑓: 0.10 (1 hom.)
• Consequence: IRGM NM_001145805.2 5_prime_UTR
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -1.89
• Publications: 9 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=-0.93).
• BA1: GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.595 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
IRGM	NM_001145805.2	c.-1103A>G		5_prime_UTR_variant	Exon 1 of 2	ENST00000522154.2	NP_001139277.1
IRGM	NR_170598.1	n.13A>G		non_coding_transcript_exon_variant	Exon 1 of 5
IRGM	NM_001346557.2	c.-1103A>G		5_prime_UTR_variant	Exon 1 of 4		NP_001333486.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
IRGM	ENST00000522154.2	c.-1103A>G		5_prime_UTR_variant	Exon 1 of 2	1	NM_001145805.2	ENSP00000428220.1

Frequencies

GnomAD3 genomes AF: 0.289 AC: 43599 AN: 150860 Hom.: 8047 Cov.: 32

Gnomad AFR AF: 0.486

Gnomad AMI AF: 0.227

Gnomad AMR AF: 0.267

Gnomad ASJ AF: 0.229

Gnomad EAS AF: 0.613

Gnomad SAS AF: 0.327

Gnomad FIN AF: 0.190

Gnomad MID AF: 0.330

Gnomad NFE AF: 0.167

Gnomad OTH AF: 0.283

GnomAD4 exome AF: 0.104 AC: 5 AN: 48 Hom.: 1 Cov.: 0 AF XY: 0.0952 AC XY: 4 AN XY: 42

African (AFR) AC: 0 AN: 0

American (AMR) AC: 0 AN: 0

Ashkenazi Jewish (ASJ) AC: 0 AN: 0

East Asian (EAS) AC: 0 AN: 0

South Asian (SAS) AC: 0 AN: 0

European-Finnish (FIN) AC: 0 AN: 0

Middle Eastern (MID) AF: 0.750 AC: 3 AN: 4

European-Non Finnish (NFE) AF: 0.0250 AC: 1 AN: 40

Other (OTH) AF: 0.250 AC: 1 AN: 4

GnomAD4 genome AF: 0.289 AC: 43664 AN: 150980 Hom.: 8068 Cov.: 32 AF XY: 0.293 AC XY: 21626 AN XY: 73804

African (AFR) AF: 0.486 AC: 19905 AN: 40956

American (AMR) AF: 0.267 AC: 4057 AN: 15190

Ashkenazi Jewish (ASJ) AF: 0.229 AC: 784 AN: 3428

East Asian (EAS) AF: 0.613 AC: 3115 AN: 5080

South Asian (SAS) AF: 0.327 AC: 1566 AN: 4794

European-Finnish (FIN) AF: 0.190 AC: 1999 AN: 10510

Middle Eastern (MID) AF: 0.328 AC: 95 AN: 290

European-Non Finnish (NFE) AF: 0.167 AC: 11343 AN: 67726

Other (OTH) AF: 0.283 AC: 593 AN: 2094

Alfa AF: 0.0867 Hom.: 114

Bravo AF: 0.308

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.93
CADD	Benign	2.6
DANN	Benign	0.47
PhyloP100		-1.9
PromoterAI		0.014	Neutral
Mutation Taster		=300/0	polymorphism (auto)

Splicing

Name	Calibrated prediction	Score	Prediction
SpliceAI score (max)		0.0		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: rs12654043; hg19: chr5-150226095;