dbSNP rs17111376: 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:

Genome browser will be placed here

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.

Transcripts

RefSeq

Gene	Transcript	HGVSc	Effect	Exon rank	MANE	Protein	UniProt
IRGM	NM_001145805.2 link	c.-416+117T>C	intron_variant	Intron 1 of 1	ENST00000522154.2	NP_001139277.1	A1A4Y4-1
IRGM	NM_001346557.2 link	c.-416+117T>C	intron_variant	Intron 1 of 3		NP_001333486.1	A1A4Y4-2
IRGM	NR_170598.1 link	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 link	c.-416+117T>C		intron_variant	Intron 1 of 1	1	NM_001145805.2	ENSP00000428220.1		A1A4Y4-1
IRGM	ENST00000609660.1 link	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.:

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 v4.3

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

Transcripts

RefSeq

Ensembl

Frequencies

Age Distribution

Age Distribution

ClinVar

Computational scores

Splicing

Publications

Other links and lift over