rs17111376

Variant names:

• chr5-150847337-T-C
• rs17111376
• NM_001145805.2:c.-416+117T>C

Your query was ambiguous. Multiple possible variants found:

• chr5-150847337-T-C
• chr5-150847337-T-G

Variant summary

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

The NM_001145805.2(IRGM):​c.-416+117T>C variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.207 in 152,254 control chromosomes in the GnomAD database, including 5,248 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 0.21 (5245 hom., cov: 32)
  • Exomes 𝑓: 0.11 (3 hom.)
• Consequence: IRGM NM_001145805.2 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -1.31

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=-1.03).
• BA1: GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.437 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
IRGM	NM_001145805.2	c.-416+117T>C		intron_variant	Intron 1 of 1	ENST00000522154.2	NP_001139277.1
IRGM	NM_001346557.2	c.-416+117T>C		intron_variant	Intron 1 of 3		NP_001333486.1
IRGM	NR_170598.1	n.700+117T>C		intron_variant	Intron 1 of 4

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
IRGM	ENST00000522154.2	c.-416+117T>C		intron_variant	Intron 1 of 1	1	NM_001145805.2	ENSP00000428220.1
IRGM	ENST00000609660.1	n.535T>C		non_coding_transcript_exon_variant	Exon 1 of 1	6

Frequencies

GnomAD3 genomes AF: 0.207 AC: 31452 AN: 151978 Hom.: 5231 Cov.: 32

Gnomad AFR AF: 0.443

Gnomad AMI AF: 0.0351

Gnomad AMR AF: 0.154

Gnomad ASJ AF: 0.164

Gnomad EAS AF: 0.433

Gnomad SAS AF: 0.211

Gnomad FIN AF: 0.0820

Gnomad MID AF: 0.206

Gnomad NFE AF: 0.0819

Gnomad OTH AF: 0.211

GnomAD4 exome AF: 0.108 AC: 17 AN: 158 Hom.: 3 Cov.: 0 AF XY: 0.140 AC XY: 12 AN XY: 86

Gnomad4 AFR exome AF: 1.00

Gnomad4 EAS exome AF: 0.100

Gnomad4 FIN exome AF: 0.00

Gnomad4 NFE exome AF: 0.100

Gnomad4 OTH exome AF: 0.00

GnomAD4 genome AF: 0.207 AC: 31505 AN: 152096 Hom.: 5245 Cov.: 32 AF XY: 0.207 AC XY: 15404 AN XY: 74384

Gnomad4 AFR AF: 0.443

Gnomad4 AMR AF: 0.154

Gnomad4 ASJ AF: 0.164

Gnomad4 EAS AF: 0.434

Gnomad4 SAS AF: 0.210

Gnomad4 FIN AF: 0.0820

Gnomad4 NFE AF: 0.0819

Gnomad4 OTH AF: 0.213

Alfa AF: 0.145 Hom.: 378

Bravo AF: 0.224

Asia WGS AF: 0.323 AC: 1123 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-1.0
CADD	Benign	2.2
DANN	Benign	0.53

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: rs17111376; hg19: chr5-150226899;