Genetic Variant NM_001145805.2:c.530G>A (chr5-150848653-G-A) – ACMG Classification: Likely_benign (-6 pts)

Variant summary

Our verdict is Likely benign. The variant received -6 ACMG points: 0P and 6B. BP4_StrongBP6_Moderate

The NM_001145805.2(IRGM):c.530G>A(p.Arg177Gln) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.000045 in 1,533,116 control chromosomes in the GnomAD database, including 1 homozygotes. In-silico tool predicts a benign outcome for this variant. 16/22 in silico tools predict a benign outcome for this variant. Variant has been reported in ClinVar as Likely benign (★).

Frequency

Genomes: 𝑓 0.000033 ( 0 hom., cov: 32)

Exomes 𝑓: 0.000046 ( 1 hom. )

Consequence

IRGM
NM_001145805.2 missense

Scores

Clinical Significance

Likely benign criteria provided, single submitter B:1

Conservation

PhyloP100: 0.491

Publications

1 publications found

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:

Genome browser will be placed here

ACMG classification

Classification was made for transcript

Our verdict: Likely_benign. The variant received -6 ACMG points.

BP4

Computational evidence support a benign effect (MetaRNN=0.035566896).

BP6

Variant 5-150848653-G-A is Benign according to our data. Variant chr5-150848653-G-A is described in ClinVar as Likely_benign. ClinVar VariationId is 2271847.Status of the report is criteria_provided_single_submitter, 1 stars.

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_001145805.2. You can select a different transcript below to see updated ACMG assignments.

RefSeq Transcripts

Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
IRGM	NM_001145805.2	MANE Select	c.530G>A	p.Arg177Gln	missense	Exon 2 of 2	NP_001139277.1	A1A4Y4-1
IRGM	NM_001346557.2		c.530G>A	p.Arg177Gln	missense splice_region	Exon 2 of 4	NP_001333486.1	A1A4Y4-2
IRGM	NR_170598.1		n.1645G>A		splice_region non_coding_transcript_exon	Exon 2 of 5

Ensembl Transcripts

Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
IRGM	ENST00000522154.2	TSL:1 MANE Select	c.530G>A	p.Arg177Gln	missense	Exon 2 of 2	ENSP00000428220.1	A1A4Y4-1
IRGM	ENST00000520549.1	TSL:1	n.155G>A		splice_region non_coding_transcript_exon	Exon 1 of 4	ENSP00000429819.1	A0A9H4B933
IRGM	ENST00000951736.1		c.530G>A	p.Arg177Gln	missense	Exon 2 of 2	ENSP00000621795.1

Frequencies

GnomAD3 genomes

AF:

0.0000329

AC:

AN:

152130

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:

0.000772

Gnomad SAS

AF:

0.00

Gnomad FIN

AF:

0.00

Gnomad MID

AF:

0.00

Gnomad NFE

AF:

0.00

Gnomad OTH

AF:

0.000478

GnomAD2 exomes

AF:

0.0000977

AC:

AN:

143348

AF XY:

0.0000656

show subpopulations

Gnomad AFR exome

AF:

0.000134

Gnomad AMR exome

AF:

0.00

Gnomad ASJ exome

AF:

0.00

Gnomad EAS exome

AF:

0.000831

Gnomad FIN exome

AF:

0.00

Gnomad NFE exome

AF:

0.0000362

Gnomad OTH exome

AF:

0.000248

GnomAD4 exome

AF:

0.0000463

AC:

AN:

1380868

Hom.:

Cov.:

AF XY:

0.0000383

AC XY:

AN XY:

678714

show subpopulations

African (AFR)

AF:

0.0000323

AC:

AN:

30936

American (AMR)

AF:

0.0000299

AC:

AN:

33484

Ashkenazi Jewish (ASJ)

AF:

0.00

AC:

AN:

24342

East Asian (EAS)

AF:

0.00101

AC:

AN:

35530

South Asian (SAS)

AF:

0.0000258

AC:

AN:

77462

European-Finnish (FIN)

AF:

0.00

AC:

AN:

48938

Middle Eastern (MID)

AF:

0.00

AC:

AN:

5600

European-Non Finnish (NFE)

AF:

0.0000187

AC:

AN:

1067482

Other (OTH)

AF:

0.0000701

AC:

AN:

57094

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.489

Heterozygous variant carriers

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Exome Het

Variant carriers

<30

30-35

35-40

40-45

45-50

50-55

55-60

60-65

65-70

70-75

75-80

>80

Age

GnomAD4 genome

AF:

0.0000328

AC:

AN:

152248

Hom.:

Cov.:

AF XY:

0.0000537

AC XY:

AN XY:

74436

show subpopulations

African (AFR)

AF:

0.00

AC:

AN:

41550

American (AMR)

AF:

0.00

AC:

AN:

15304

Ashkenazi Jewish (ASJ)

AF:

0.00

AC:

AN:

3470

East Asian (EAS)

AF:

0.000773

AC:

AN:

5172

South Asian (SAS)

AF:

0.00

AC:

AN:

4818

European-Finnish (FIN)

AF:

0.00

AC:

AN:

10604

Middle Eastern (MID)

AF:

0.00

AC:

AN:

294

European-Non Finnish (NFE)

AF:

0.00

AC:

AN:

68010

Other (OTH)

AF:

0.000473

AC:

AN:

2114

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.485

Heterozygous variant carriers

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Genome Het

Variant carriers

<30

30-35

35-40

40-45

45-50

50-55

55-60

60-65

65-70

70-75

75-80

>80

Age

Alfa

AF:

0.0000712

Hom.:

Bravo

AF:

0.0000567

ExAC

AF:

0.0000445

AC:

ClinVar

ClinVar submissions

Significance:Likely benign

Revision:criteria provided, single submitter

View on ClinVar

Pathogenic

VUS

Benign

Condition

not specified (1)

Computational scores

Source: dbNSFP v4.9

Name

Calibrated prediction

Score

Prediction

AlphaMissense

Benign

0.073

BayesDel_addAF

Benign

-0.55

BayesDel_noAF

Benign

-0.64

CADD

Benign

0.58

(source)

DANN

Benign

0.45

DEOGEN2

Benign

0.050

Eigen

Benign

-1.6

Eigen_PC

Benign

-1.7

FATHMM_MKL

Benign

0.0015

LIST_S2

Benign

0.46

M_CAP

Benign

0.0078

MetaRNN

Benign

0.036

MetaSVM

Benign

-1.0

MutationAssessor

Benign

0.37

PhyloP100

0.49

PrimateAI

Benign

0.20

PROVEAN

Benign

-0.41

REVEL

Benign

0.019

Sift

Benign

0.38

Sift4G

Benign

0.35

Polyphen

0.32

Vest4

0.021

MutPred

0.61

Gain of ubiquitination at K175 (P = 0.1222)

MVP

0.014

ClinPred

0.0029

GERP RS

-3.6

Varity_R

0.032

gMVP

0.18

Mutation Taster

=97/3

polymorphism

(source)

Splicing

Name

Calibrated prediction

Score

Prediction

SpliceAI score (max)

0.010

Details are displayed if max score is > 0.2

Find out detailed SpliceAI scores and Pangolin per-transcript scores at spliceailookup.broadinstitute.org

Publications

You must be logged in to view publications. This limit was set because tens of millions (!) of queries from AI bots are generated daily.

Variant summary

Frequency

Consequence

Scores

Clinical Significance

Conservation

Publications

ACMG classification

Variant Effect in Transcripts

RefSeq Transcripts

Ensembl Transcripts

Frequencies

Age Distribution

Age Distribution

ClinVar

Computational scores

Splicing

Publications

Other links and lift over