dbSNP rs10059011: IRGM:c.-476A>C (chr5-150847160-A-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.-476A>C variant causes a 5 prime UTR change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.529 in 152,154 control chromosomes in the GnomAD database, including 21,478 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 0.53 ( 21444 hom., cov: 31)

Exomes 𝑓: 0.58 ( 34 hom. )

Consequence

IRGM
NM_001145805.2 5_prime_UTR

Scores

Clinical Significance

Not reported in ClinVar

Conservation

PhyloP100: -0.306

Publications

13 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=-1.0).

BA1

GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.553 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	Effect	Exon rank	MANE	Protein	UniProt
IRGM	NM_001145805.2 link	c.-476A>C	5_prime_UTR_variant	Exon 1 of 2	ENST00000522154.2	NP_001139277.1	A1A4Y4-1
IRGM	NR_170598.1 link	n.640A>C	non_coding_transcript_exon_variant	Exon 1 of 5
IRGM	NM_001346557.2 link	c.-476A>C	5_prime_UTR_variant	Exon 1 of 4		NP_001333486.1	A1A4Y4-2

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
IRGM	ENST00000522154.2 link	c.-476A>C		5_prime_UTR_variant	Exon 1 of 2	1	NM_001145805.2	ENSP00000428220.1		A1A4Y4-1
IRGM	ENST00000609660.1 link	n.358A>C		non_coding_transcript_exon_variant	Exon 1 of 1	6

Frequencies

GnomAD3 genomes

AF:

0.529

AC:

80286

AN:

151838

Hom.:

21432

Cov.:

show subpopulations

Gnomad AFR

AF:

0.559

Gnomad AMI

AF:

0.359

Gnomad AMR

AF:

0.421

Gnomad ASJ

AF:

0.464

Gnomad EAS

AF:

0.442

Gnomad SAS

AF:

0.415

Gnomad FIN

AF:

0.555

Gnomad MID

AF:

0.443

Gnomad NFE

AF:

0.551

Gnomad OTH

AF:

0.530

GnomAD4 exome

AF:

0.581

AC:

115

AN:

198

Hom.:

Cov.:

AF XY:

0.576

AC XY:

AN XY:

118

show subpopulations

African (AFR)

AC:

AN:

American (AMR)

AC:

AN:

Ashkenazi Jewish (ASJ)

AF:

0.750

AC:

AN:

East Asian (EAS)

AF:

0.559

AC:

AN:

136

South Asian (SAS)

AF:

1.00

AC:

AN:

European-Finnish (FIN)

AF:

0.750

AC:

AN:

Middle Eastern (MID)

AC:

AN:

European-Non Finnish (NFE)

AF:

0.604

AC:

AN:

Other (OTH)

AF:

0.500

AC:

AN:

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.501

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:

0.529

AC:

80340

AN:

151956

Hom.:

21444

Cov.:

AF XY:

0.521

AC XY:

38675

AN XY:

74300

show subpopulations

African (AFR)

AF:

0.559

AC:

23139

AN:

41414

American (AMR)

AF:

0.420

AC:

6424

AN:

15278

Ashkenazi Jewish (ASJ)

AF:

0.464

AC:

1609

AN:

3470

East Asian (EAS)

AF:

0.442

AC:

2284

AN:

5162

South Asian (SAS)

AF:

0.414

AC:

1990

AN:

4808

European-Finnish (FIN)

AF:

0.555

AC:

5863

AN:

10564

Middle Eastern (MID)

AF:

0.463

AC:

136

AN:

294

European-Non Finnish (NFE)

AF:

0.551

AC:

37458

AN:

67956

Other (OTH)

AF:

0.529

AC:

1112

AN:

2104

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.503

Heterozygous variant carriers

1892

3784

5676

7568

9460

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Genome Het

Genome Hom

Variant carriers

708

1416

2124

2832

3540

<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:

0.538

Hom.:

77768

Bravo

AF:

0.520

Asia WGS

AF:

0.436

AC:

1515

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

3.7

(source)

DANN

Benign

0.52

PhyloP100

-0.31

Mutation Taster

=300/0

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