chr5-150848235-A-G

Variant summary

Our verdict is Likely benign. Variant got -4 ACMG points: 2P and 6B. PM2BP4_StrongBP6_Moderate

The NM_001145805.2(IRGM):ā€‹c.112A>Gā€‹(p.Met38Val) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0000122 in 1,551,722 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a benign outcome for this variant. 15/20 in silico tools predict a benign outcome for this variant. Variant has been reported in ClinVar as Likely benign (ā˜…).

Frequency

Genomes: š‘“ 0.0000066 ( 0 hom., cov: 32)
Exomes š‘“: 0.000013 ( 0 hom. )

Consequence

IRGM
NM_001145805.2 missense

Scores

19

Clinical Significance

Likely benign criteria provided, single submitter B:1

Conservation

PhyloP100: 0.944
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]

Genome browser will be placed here

ACMG classification

Classification made for transcript

Verdict is Likely_benign. Variant got -4 ACMG points.

PM2
Very rare variant in population databases, with high coverage;
BP4
Computational evidence support a benign effect (MetaRNN=0.0573875).
BP6
Variant 5-150848235-A-G is Benign according to our data. Variant chr5-150848235-A-G is described in ClinVar as [Likely_benign]. Clinvar id is 2273698.Status of the report is criteria_provided_single_submitter, 1 stars.

Transcripts

RefSeq

Gene Transcript HGVSc HGVSp Effect #exon/exons MANE Protein UniProt
IRGMNM_001145805.2 linkuse as main transcriptc.112A>G p.Met38Val missense_variant 2/2 ENST00000522154.2 NP_001139277.1
IRGMNM_001346557.2 linkuse as main transcriptc.112A>G p.Met38Val missense_variant 2/4 NP_001333486.1
IRGMNR_170598.1 linkuse as main transcriptn.1227A>G non_coding_transcript_exon_variant 2/5

Ensembl

Gene Transcript HGVSc HGVSp Effect #exon/exons TSL MANE Protein Appris UniProt
IRGMENST00000522154.2 linkuse as main transcriptc.112A>G p.Met38Val missense_variant 2/21 NM_001145805.2 ENSP00000428220 P1

Frequencies

GnomAD3 genomes
AF:
0.00000657
AC:
1
AN:
152206
Hom.:
0
Cov.:
32
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:
0.00
Gnomad FIN
AF:
0.00
Gnomad MID
AF:
0.00
Gnomad NFE
AF:
0.0000147
Gnomad OTH
AF:
0.00
GnomAD3 exomes
AF:
0.0000195
AC:
3
AN:
154212
Hom.:
0
AF XY:
0.0000122
AC XY:
1
AN XY:
81840
show subpopulations
Gnomad AFR exome
AF:
0.00
Gnomad AMR exome
AF:
0.0000810
Gnomad ASJ exome
AF:
0.00
Gnomad EAS exome
AF:
0.00
Gnomad SAS exome
AF:
0.00
Gnomad FIN exome
AF:
0.00
Gnomad NFE exome
AF:
0.0000168
Gnomad OTH exome
AF:
0.00
GnomAD4 exome
AF:
0.0000129
AC:
18
AN:
1399516
Hom.:
0
Cov.:
32
AF XY:
0.0000130
AC XY:
9
AN XY:
690278
show subpopulations
Gnomad4 AFR exome
AF:
0.00
Gnomad4 AMR exome
AF:
0.000112
Gnomad4 ASJ exome
AF:
0.00
Gnomad4 EAS exome
AF:
0.00
Gnomad4 SAS exome
AF:
0.00
Gnomad4 FIN exome
AF:
0.00
Gnomad4 NFE exome
AF:
0.00000927
Gnomad4 OTH exome
AF:
0.0000690
GnomAD4 genome
AF:
0.00000657
AC:
1
AN:
152206
Hom.:
0
Cov.:
32
AF XY:
0.0000134
AC XY:
1
AN XY:
74354
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:
0.00
Gnomad4 FIN
AF:
0.00
Gnomad4 NFE
AF:
0.0000147
Gnomad4 OTH
AF:
0.00
Bravo
AF:
0.0000189

ClinVar

Significance: Likely benign
Submissions summary: Benign:1
Revision: criteria provided, single submitter
LINK: link

Submissions by phenotype

not specified Benign:1
Likely benign, criteria provided, single submitterclinical testingAmbry GeneticsSep 16, 2021This alteration is classified as likely benign based on a combination of the following: seen in unaffected individuals, population frequency, intact protein function, lack of segregation with disease, co-occurrence, RNA analysis, in silico models, amino acid conservation, lack of disease association in case-control studies, and/or the mechanism of disease or impacted region is inconsistent with a known cause of pathogenicity. -

Computational scores

Source: dbNSFP v4.3

Name
Calibrated prediction
Score
Prediction
AlphaMissense
Benign
0.049
BayesDel_addAF
Benign
-0.48
T
BayesDel_noAF
Benign
-0.74
CADD
Benign
0.16
DANN
Benign
0.24
DEOGEN2
Benign
0.044
T
Eigen
Benign
-1.5
Eigen_PC
Benign
-1.3
FATHMM_MKL
Benign
0.0082
N
LIST_S2
Benign
0.54
T
M_CAP
Benign
0.017
T
MetaRNN
Benign
0.057
T
MetaSVM
Benign
-0.95
T
MutationAssessor
Benign
-3.4
N
MutationTaster
Benign
1.0
N
PrimateAI
Benign
0.25
T
PROVEAN
Benign
2.4
N
REVEL
Benign
0.13
Sift
Benign
1.0
T
Sift4G
Benign
1.0
T
Polyphen
0.0010
B
Vest4
0.12
MutPred
0.55
Loss of catalytic residue at V34 (P = 0.0171);
MVP
0.014
ClinPred
0.047
T
GERP RS
2.9
Varity_R
0.041
gMVP
0.11

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.

Other links and lift over

dbSNP: rs1473059816; hg19: chr5-150227797; API