Variant chr5-150848296-A-G details in Genebe, Genetics Data Aggregator

Variant summary

Our verdict is Benign. Variant got -8 ACMG points: 0P and 8B. BP4_StrongBS2

The NM_001145805.2(IRGM):c.173A>G(p.His58Arg) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.000175 in 1,551,836 control chromosomes in the GnomAD database, including 2 homozygotes. In-silico tool predicts a benign outcome for this variant. 13/20 in silico tools predict a benign outcome for this variant. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar.

Frequency

Genomes: 𝑓 0.00013 ( 0 hom., cov: 32)

Exomes 𝑓: 0.00018 ( 2 hom. )

Consequence

IRGM
NM_001145805.2 missense

Scores

Clinical Significance

Not reported in ClinVar

Conservation

PhyloP100: 2.74

Variant links:

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 links:

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ACMG classification

Classification made for transcript

Verdict is Benign. Variant got -8 ACMG points.

BP4

Computational evidence support a benign effect (MetaRNN=0.017193645).

BS2

High Homozygotes in GnomAdExome4 at 2 AR gene

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein
IRGM	NM_001145805.2 linkuse as main transcript	c.173A>G	p.His58Arg	missense_variant	2/2	ENST00000522154.2	NP_001139277.1
IRGM	NM_001346557.2 linkuse as main transcript	c.173A>G	p.His58Arg	missense_variant	2/4		NP_001333486.1
IRGM	NR_170598.1 linkuse as main transcript	n.1288A>G		non_coding_transcript_exon_variant	2/5

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
IRGM	ENST00000522154.2 linkuse as main transcript	c.173A>G	p.His58Arg	missense_variant	2/2	1	NM_001145805.2	ENSP00000428220	P1

Frequencies

GnomAD3 genomes

AF:

0.000125

AC:

AN:

152180

Hom.:

Cov.:

show subpopulations

Gnomad AFR

AF:

0.00

Gnomad AMI

AF:

0.00

Gnomad AMR

AF:

0.00

Gnomad ASJ

AF:

0.00

Gnomad EAS

AF:

0.00

Gnomad SAS

AF:

0.00373

Gnomad FIN

AF:

0.00

Gnomad MID

AF:

0.00

Gnomad NFE

AF:

0.00

Gnomad OTH

AF:

0.000479

GnomAD3 exomes

AF:

0.000408

AC:

AN:

154276

Hom.:

AF XY:

0.000501

AC XY:

AN XY:

81846

show subpopulations

Gnomad AFR exome

AF:

0.00

Gnomad AMR exome

AF:

0.00

Gnomad ASJ exome

AF:

0.00

Gnomad EAS exome

AF:

0.00

Gnomad SAS exome

AF:

0.00272

Gnomad FIN exome

AF:

0.00

Gnomad NFE exome

AF:

0.00

Gnomad OTH exome

AF:

0.000230

GnomAD4 exome

AF:

0.000180

AC:

252

AN:

1399538

Hom.:

Cov.:

AF XY:

0.000248

AC XY:

171

AN XY:

690286

show subpopulations

Gnomad4 AFR exome

AF:

0.00

Gnomad4 AMR exome

AF:

0.00

Gnomad4 ASJ exome

AF:

0.00

Gnomad4 EAS exome

AF:

0.00

Gnomad4 SAS exome

AF:

0.00289

Gnomad4 FIN exome

AF:

0.00

Gnomad4 NFE exome

AF:

0.00000371

Gnomad4 OTH exome

AF:

0.000328

GnomAD4 genome

AF:

0.000131

AC:

AN:

152298

Hom.:

Cov.:

AF XY:

0.000215

AC XY:

AN XY:

74476

show subpopulations

Gnomad4 AFR

AF:

0.00

Gnomad4 AMR

AF:

0.00

Gnomad4 ASJ

AF:

0.00

Gnomad4 EAS

AF:

0.00

Gnomad4 SAS

AF:

0.00394

Gnomad4 FIN

AF:

0.00

Gnomad4 NFE

AF:

0.00

Gnomad4 OTH

AF:

0.000474

Bravo

AF:

0.0000227

ExAC

AF:

0.000895

AC:

Asia WGS

AF:

0.00144

AC:

AN:

3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

AlphaMissense

Benign

0.081

BayesDel_addAF

Benign

-0.47

BayesDel_noAF

Benign

-0.45

CADD

Benign

DANN

Benign

0.97

DEOGEN2

Benign

0.24

Eigen

Benign

-0.0076

Eigen_PC

Benign

-0.26

FATHMM_MKL

Benign

0.12

LIST_S2

Benign

0.46

M_CAP

Benign

0.013

MetaRNN

Benign

0.017

MetaSVM

Benign

-0.97

MutationAssessor

Pathogenic

3.3

MutationTaster

Benign

1.0

PrimateAI

Benign

0.29

PROVEAN

Pathogenic

-6.5

REVEL

Benign

0.070

Sift

Uncertain

0.0060

Sift4G

Pathogenic

0.0

Polyphen

1.0

Vest4

0.072

MutPred

0.71

Gain of MoRF binding (P = 0.0166);

MVP

0.048

ClinPred

0.37

GERP RS

2.3

Varity_R

0.62

gMVP

0.070

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

Below is the list of publications found by LitVar. It may be empty.

Variant summary

Frequency

Consequence

Scores

Clinical Significance

Conservation

ACMG classification

Transcripts

RefSeq

Ensembl

Frequencies

ClinVar

Computational scores

Splicing

Publications

LitVar

Other links and lift over