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.

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.-476A>C	5_prime_UTR	Exon 1 of 2	NP_001139277.1
IRGM	NR_170598.1		n.640A>C	non_coding_transcript_exon	Exon 1 of 5
IRGM	NM_001346557.2		c.-476A>C	5_prime_UTR	Exon 1 of 4	NP_001333486.1

Ensembl Transcripts

Selected	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	IRGM	ENST00000522154.2	TSL:1 MANE Select	c.-476A>C		5_prime_UTR	Exon 1 of 2	ENSP00000428220.1
	IRGM	ENST00000609660.1	TSL:6	n.358A>C		non_coding_transcript_exon	Exon 1 of 1

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 v4.9

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

Variant Effect in Transcripts

RefSeq Transcripts

Ensembl Transcripts

Frequencies

Age Distribution

Age Distribution

ClinVar

Computational scores

Splicing

Publications

Other links and lift over