5-150846642-T-C

Position:

• chr5-150846642-T-C

Variant summary

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

The NM_001145805.2(IRGM):​c.-994T>C variant causes a 5 prime UTR change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.202 in 150,926 control chromosomes in the GnomAD database, including 5,195 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 0.20 (5195 hom., cov: 32)
  • Exomes 𝑓: 0.031 (0 hom.)
• Consequence: IRGM NM_001145805.2 5_prime_UTR
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -1.45

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]

IRGM (HGNC:):

ACMG classification

Verdict is Benign. Variant got -12 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.95).
• BA1: GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.432 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
IRGM	NM_001145805.2	c.-994T>C		5_prime_UTR_variant	1/2	ENST00000522154.2	NP_001139277.1
IRGM	NM_001346557.2	c.-994T>C		5_prime_UTR_variant	1/4		NP_001333486.1
IRGM	NR_170598.1	n.122T>C		non_coding_transcript_exon_variant	1/5

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
IRGM	ENST00000522154	c.-994T>C		5_prime_UTR_variant	1/2	1	NM_001145805.2	ENSP00000428220.1

Frequencies

GnomAD3 genomes AF: 0.202 AC: 30381 AN: 150704 Hom.: 5181 Cov.: 32

Gnomad AFR AF: 0.437

Gnomad AMI AF: 0.0319

Gnomad AMR AF: 0.149

Gnomad ASJ AF: 0.160

Gnomad EAS AF: 0.422

Gnomad SAS AF: 0.199

Gnomad FIN AF: 0.0773

Gnomad MID AF: 0.188

Gnomad NFE AF: 0.0787

Gnomad OTH AF: 0.205

GnomAD4 exome AF: 0.0313 AC: 3 AN: 96 Hom.: 0 Cov.: 0 AF XY: 0.0405 AC XY: 3 AN XY: 74

Gnomad4 ASJ exome AF: 0.00

Gnomad4 SAS exome AF: 0.250

Gnomad4 FIN exome AF: 0.00

Gnomad4 NFE exome AF: 0.0238

Gnomad4 OTH exome AF: 0.00

GnomAD4 genome AF: 0.202 AC: 30436 AN: 150830 Hom.: 5195 Cov.: 32 AF XY: 0.202 AC XY: 14860 AN XY: 73718

Gnomad4 AFR AF: 0.437

Gnomad4 AMR AF: 0.148

Gnomad4 ASJ AF: 0.160

Gnomad4 EAS AF: 0.423

Gnomad4 SAS AF: 0.198

Gnomad4 FIN AF: 0.0773

Gnomad4 NFE AF: 0.0787

Gnomad4 OTH AF: 0.207

Alfa AF: 0.0316 Hom.: 38

Bravo AF: 0.224

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.95
CADD	Benign	3.9
DANN	Benign	0.14

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

Publications

LitVar

Other links and lift over

dbSNP: rs35898555; hg19: chr5-150226204;