dbSNP rs17111379: IRGM:c.-415-151G>C (chr5-150847558-G-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.-415-151G>C variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0547 in 153,366 control chromosomes in the GnomAD database, including 784 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 0.055 ( 784 hom., cov: 32)

Exomes 𝑓: 0.0026 ( 0 hom. )

Consequence

IRGM
NM_001145805.2 intron

Scores

Clinical Significance

Not reported in ClinVar

Conservation

PhyloP100: 1.28

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: Benign. The variant received -12 ACMG points.

BP4

Computational evidence support a benign effect (BayesDel_noAF=-0.89).

BA1

GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.188 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	Effect	Exon rank	MANE	Protein	UniProt
IRGM	NM_001145805.2 link	c.-415-151G>C	intron_variant	Intron 1 of 1	ENST00000522154.2	NP_001139277.1	A1A4Y4-1
IRGM	NM_001346557.2 link	c.-415-151G>C	intron_variant	Intron 1 of 3		NP_001333486.1	A1A4Y4-2
IRGM	NR_170598.1 link	n.701-151G>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.-415-151G>C		intron_variant	Intron 1 of 1	1	NM_001145805.2	ENSP00000428220.1		A1A4Y4-1
IRGM	ENST00000609660.1 link	n.*71G>C		downstream_gene_variant		6

Frequencies

GnomAD3 genomes

AF:

0.0551

AC:

8375

AN:

152084

Hom.:

781

Cov.:

show subpopulations

Gnomad AFR

AF:

0.192

Gnomad AMI

AF:

0.00

Gnomad AMR

AF:

0.0212

Gnomad ASJ

AF:

0.00

Gnomad EAS

AF:

0.00

Gnomad SAS

AF:

0.00145

Gnomad FIN

AF:

0.00

Gnomad MID

AF:

0.0158

Gnomad NFE

AF:

0.000617

Gnomad OTH

AF:

0.0354

GnomAD4 exome

AF:

0.00258

AC:

AN:

1164

Hom.:

Cov.:

AF XY:

0.00163

AC XY:

AN XY:

612

show subpopulations

African (AFR)

AF:

0.00

AC:

AN:

American (AMR)

AF:

0.0125

AC:

AN:

160

Ashkenazi Jewish (ASJ)

AF:

0.00

AC:

AN:

East Asian (EAS)

AF:

0.00725

AC:

AN:

138

South Asian (SAS)

AF:

0.00

AC:

AN:

European-Finnish (FIN)

AF:

0.00

AC:

AN:

Middle Eastern (MID)

AC:

AN:

European-Non Finnish (NFE)

AF:

0.00

AC:

AN:

794

Other (OTH)

AF:

0.00

AC:

AN:

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.625

Heterozygous variant carriers

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

GnomAD4 genome

AF:

0.0551

AC:

8391

AN:

152202

Hom.:

784

Cov.:

AF XY:

0.0534

AC XY:

3973

AN XY:

74446

show subpopulations

African (AFR)

AF:

0.192

AC:

7941

AN:

41460

American (AMR)

AF:

0.0212

AC:

324

AN:

15304

Ashkenazi Jewish (ASJ)

AF:

0.00

AC:

AN:

3472

East Asian (EAS)

AF:

0.00

AC:

AN:

5182

South Asian (SAS)

AF:

0.00124

AC:

AN:

4830

European-Finnish (FIN)

AF:

0.00

AC:

AN:

10614

Middle Eastern (MID)

AF:

0.0136

AC:

AN:

294

European-Non Finnish (NFE)

AF:

0.000617

AC:

AN:

68024

Other (OTH)

AF:

0.0351

AC:

AN:

2110

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.502

Heterozygous variant carriers

349

697

1046

1394

1743

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Alfa

AF:

0.0438

Hom.:

Bravo

AF:

0.0633

Asia WGS

AF:

0.0130

AC:

AN:

3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

BayesDel_noAF

Benign

-0.89

CADD

Benign

3.0

(source)

DANN

Benign

0.45

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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rs17111379

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