rs10052068

Positions:

• chr5-150847280-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.-416+60T>C variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0412 in 152,314 control chromosomes in the GnomAD database, including 416 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 0.041 (416 hom., cov: 32)
  • Exomes 𝑓: 0.0 (0 hom.)
  • Failed GnomAD Quality Control
• Consequence: IRGM NM_001145805.2 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.0570

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=-0.98).
• BA1: GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.14 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
IRGM	NM_001145805.2	c.-416+60T>C		intron_variant		ENST00000522154.2
IRGM	NM_001346557.2	c.-416+60T>C		intron_variant
IRGM	NR_170598.1	n.700+60T>C		intron_variant, non_coding_transcript_variant

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
IRGM	ENST00000522154.2	c.-416+60T>C		intron_variant		1	NM_001145805.2	P1
IRGM	ENST00000609660.1	n.478T>C		non_coding_transcript_exon_variant	1/1

Frequencies

GnomAD3 genomes AF: 0.0410 AC: 6240 AN: 152196 Hom.: 410 Cov.: 32

Gnomad AFR AF: 0.143

Gnomad AMI AF: 0.00

Gnomad AMR AF: 0.0119

Gnomad ASJ AF: 0.00

Gnomad EAS AF: 0.00115

Gnomad SAS AF: 0.00496

Gnomad FIN AF: 0.00

Gnomad MID AF: 0.00316

Gnomad NFE AF: 0.000470

Gnomad OTH AF: 0.0330

GnomAD4 exome Data not reliable, filtered out with message: AC0 AF: 0.00 AC: 0 AN: 202 Hom.: 0 Cov.: 0 AF XY: 0.00 AC XY: 0 AN XY: 122

Gnomad4 AFR exome AF: 0.00

Gnomad4 EAS exome AF: 0.00

Gnomad4 FIN exome AF: 0.00

Gnomad4 NFE exome AF: 0.00

Gnomad4 OTH exome AF: 0.00

GnomAD4 genome AF: 0.0412 AC: 6275 AN: 152314 Hom.: 416 Cov.: 32 AF XY: 0.0400 AC XY: 2976 AN XY: 74492

Gnomad4 AFR AF: 0.143

Gnomad4 AMR AF: 0.0118

Gnomad4 ASJ AF: 0.00

Gnomad4 EAS AF: 0.00116

Gnomad4 SAS AF: 0.00518

Gnomad4 FIN AF: 0.00

Gnomad4 NFE AF: 0.000470

Gnomad4 OTH AF: 0.0336

Alfa AF: 0.00834 Hom.: 92

Bravo AF: 0.0462

Asia WGS AF: 0.0220 AC: 76 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.98
CADD	Benign	6.6
DANN	Benign	0.73

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: rs10052068; hg19: chr5-150226842;