ENST00000522154:c.-420A>C

Variant names:

• chr5-150847216-A-C
• rs77724219
• ENST00000522154:c.-420A>C

Variant summary

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

The ENST00000522154(IRGM):​c.-420A>C variant causes a 5 prime UTR premature start codon gain change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0389 in 152,436 control chromosomes in the GnomAD database, including 193 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 0.039 (193 hom., cov: 32)
  • Exomes 𝑓: 0.055 (0 hom.)
• Consequence: IRGM ENST00000522154 5_prime_UTR_premature_start_codon_gain
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.356

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

Verdict is Benign. Variant got -12 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.99).
• BA1: GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.171 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
IRGM	NM_001145805.2	c.-420A>C		5_prime_UTR_premature_start_codon_gain_variant	Exon 1 of 2	ENST00000522154.2	NP_001139277.1
IRGM	NM_001145805.2	c.-420A>C		5_prime_UTR_variant	Exon 1 of 2	ENST00000522154.2	NP_001139277.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
IRGM	ENST00000522154	c.-420A>C		5_prime_UTR_premature_start_codon_gain_variant	Exon 1 of 2	1	NM_001145805.2	ENSP00000428220.1
IRGM	ENST00000522154	c.-420A>C		5_prime_UTR_variant	Exon 1 of 2	1	NM_001145805.2	ENSP00000428220.1
IRGM	ENST00000609660.1	n.414A>C		non_coding_transcript_exon_variant	Exon 1 of 1	6

Frequencies

GnomAD3 genomes AF: 0.0389 AC: 5921 AN: 152118 Hom.: 194 Cov.: 32

Gnomad AFR AF: 0.0149

Gnomad AMI AF: 0.126

Gnomad AMR AF: 0.0305

Gnomad ASJ AF: 0.0369

Gnomad EAS AF: 0.181

Gnomad SAS AF: 0.0627

Gnomad FIN AF: 0.0328

Gnomad MID AF: 0.102

Gnomad NFE AF: 0.0425

Gnomad OTH AF: 0.0388

GnomAD4 exome AF: 0.0550 AC: 11 AN: 200 Hom.: 0 Cov.: 0 AF XY: 0.0431 AC XY: 5 AN XY: 116

Gnomad4 EAS exome AF: 0.0429

Gnomad4 FIN exome AF: 0.0714

Gnomad4 NFE exome AF: 0.0526

Gnomad4 OTH exome AF: 0.250

GnomAD4 genome AF: 0.0389 AC: 5917 AN: 152236 Hom.: 193 Cov.: 32 AF XY: 0.0404 AC XY: 3008 AN XY: 74440

Gnomad4 AFR AF: 0.0149

Gnomad4 AMR AF: 0.0305

Gnomad4 ASJ AF: 0.0369

Gnomad4 EAS AF: 0.181

Gnomad4 SAS AF: 0.0627

Gnomad4 FIN AF: 0.0328

Gnomad4 NFE AF: 0.0425

Gnomad4 OTH AF: 0.0379

Alfa AF: 0.0362 Hom.: 17

Bravo AF: 0.0395

Asia WGS AF: 0.0920 AC: 320 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.99
CADD	Benign	2.3
DANN	Benign	0.63

Splicing

Name	Calibrated prediction	Score	Prediction
SpliceAI score (max)		0.030		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: rs77724219; hg19: chr5-150226778;