Genetic Variant IRGM:c.-416+117T>C (chr5-150847337-T-C) – ACMG Classification: Benign (-12 pts)

Variant summary

Our verdict is Benign. The variant received -12 ACMG points: 0P and 12B. BP4_StrongBA1

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

Scores

Clinical Significance

Not reported in ClinVar

Conservation

PhyloP100: -1.31

Publications

9 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:

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ACMG classification

Classification was made for transcript

Our verdict: Benign. The variant received -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.

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	Effect	Exon Rank	Protein
IRGM	NM_001145805.2	MANE Select	c.-416+117T>C	intron	N/A	NP_001139277.1
IRGM	NM_001346557.2		c.-416+117T>C	intron	N/A	NP_001333486.1
IRGM	NR_170598.1		n.700+117T>C	intron	N/A

Ensembl Transcripts

Selected	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	IRGM	ENST00000522154.2	TSL:1 MANE Select	c.-416+117T>C		intron	N/A	ENSP00000428220.1
	IRGM	ENST00000609660.1	TSL:6	n.535T>C		non_coding_transcript_exon	Exon 1 of 1

Frequencies

GnomAD3 genomes

AF:

0.207

AC:

31452

AN:

151978

Hom.:

5231

Cov.:

show subpopulations

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:

AN:

158

Hom.:

Cov.:

AF XY:

0.140

AC XY:

AN XY:

show subpopulations

African (AFR)

AF:

1.00

AC:

AN:

American (AMR)

AC:

AN:

Ashkenazi Jewish (ASJ)

AC:

AN:

East Asian (EAS)

AF:

0.100

AC:

AN:

130

South Asian (SAS)

AC:

AN:

European-Finnish (FIN)

AF:

0.00

AC:

AN:

Middle Eastern (MID)

AC:

AN:

European-Non Finnish (NFE)

AF:

0.100

AC:

AN:

Other (OTH)

AF:

0.00

AC:

AN:

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.466

Heterozygous variant carriers

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Exome Het

Exome Hom

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:

0.207

AC:

31505

AN:

152096

Hom.:

5245

Cov.:

AF XY:

0.207

AC XY:

15404

AN XY:

74384

show subpopulations

African (AFR)

AF:

0.443

AC:

18346

AN:

41442

American (AMR)

AF:

0.154

AC:

2353

AN:

15274

Ashkenazi Jewish (ASJ)

AF:

0.164

AC:

569

AN:

3468

East Asian (EAS)

AF:

0.434

AC:

2243

AN:

5172

South Asian (SAS)

AF:

0.210

AC:

1011

AN:

4822

European-Finnish (FIN)

AF:

0.0820

AC:

870

AN:

10612

Middle Eastern (MID)

AF:

0.211

AC:

AN:

294

European-Non Finnish (NFE)

AF:

0.0819

AC:

5570

AN:

67988

Other (OTH)

AF:

0.213

AC:

449

AN:

2112

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.503

Heterozygous variant carriers

1115

2230

3344

4459

5574

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Genome Het

Genome Hom

Variant carriers

302

604

906

1208

1510

<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:

0.145

Hom.:

378

Bravo

AF:

0.224

Asia WGS

AF:

0.323

AC:

1123

AN:

3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name

Calibrated prediction

Score

Prediction

BayesDel_noAF

Benign

-1.0

CADD

Benign

2.2

(source)

DANN

Benign

0.53

PhyloP100

-1.3

Mutation Taster

=100/0

polymorphism (auto)

(source)

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

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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