dbSNP rs10058943: IRGM:c.-612A>G (chr5-150847024-A-G) – 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.-612A>G variant causes a 5 prime UTR change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.207 in 152,318 control chromosomes in the GnomAD database, including 5,253 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 ( 5250 hom., cov: 32)

Exomes 𝑓: 0.11 ( 3 hom. )

Consequence

IRGM
NM_001145805.2 5_prime_UTR

Scores

Clinical Significance

Not reported in ClinVar

Conservation

PhyloP100: -0.628

Publications

14 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 = 0.437 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	UniProt
IRGM	NM_001145805.2	MANE Select	c.-612A>G	5_prime_UTR	Exon 1 of 2	NP_001139277.1	A1A4Y4-1
IRGM	NM_001346557.2		c.-612A>G	5_prime_UTR	Exon 1 of 4	NP_001333486.1	A1A4Y4-2
IRGM	NR_170598.1		n.504A>G	non_coding_transcript_exon	Exon 1 of 5

Ensembl Transcripts

Gene	Transcript	Tags	HGVSc	Effect	Exon Rank	Protein	UniProt
IRGM	ENST00000522154.2	TSL:1 MANE Select	c.-612A>G	5_prime_UTR	Exon 1 of 2	ENSP00000428220.1	A1A4Y4-1
IRGM	ENST00000951736.1		c.-473A>G	5_prime_UTR	Exon 1 of 2	ENSP00000621795.1
IRGM	ENST00000609660.1	TSL:6	n.222A>G	non_coding_transcript_exon	Exon 1 of 1

Frequencies

GnomAD3 genomes

AF:

0.207

AC:

31466

AN:

152030

Hom.:

5236

Cov.:

show subpopulations

Gnomad AFR

AF:

0.442

Gnomad AMI

AF:

0.0351

Gnomad AMR

AF:

0.155

Gnomad ASJ

AF:

0.164

Gnomad EAS

AF:

0.434

Gnomad SAS

AF:

0.211

Gnomad FIN

AF:

0.0822

Gnomad MID

AF:

0.206

Gnomad NFE

AF:

0.0819

Gnomad OTH

AF:

0.210

GnomAD4 exome

AF:

0.106

AC:

AN:

170

Hom.:

Cov.:

AF XY:

0.125

AC XY:

AN XY:

104

show subpopulations

African (AFR)

AC:

AN:

American (AMR)

AF:

0.00

AC:

AN:

Ashkenazi Jewish (ASJ)

AC:

AN:

East Asian (EAS)

AF:

0.116

AC:

AN:

138

South Asian (SAS)

AC:

AN:

European-Finnish (FIN)

AF:

0.167

AC:

AN:

Middle Eastern (MID)

AC:

AN:

European-Non Finnish (NFE)

AF:

0.0417

AC:

AN:

Other (OTH)

AC:

AN:

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.463

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:

31519

AN:

152148

Hom.:

5250

Cov.:

AF XY:

0.207

AC XY:

15414

AN XY:

74402

show subpopulations

African (AFR)

AF:

0.442

AC:

18342

AN:

41454

American (AMR)

AF:

0.154

AC:

2360

AN:

15298

Ashkenazi Jewish (ASJ)

AF:

0.164

AC:

570

AN:

3470

East Asian (EAS)

AF:

0.435

AC:

2249

AN:

5172

South Asian (SAS)

AF:

0.210

AC:

1011

AN:

4818

European-Finnish (FIN)

AF:

0.0822

AC:

873

AN:

10614

Middle Eastern (MID)

AF:

0.211

AC:

AN:

294

European-Non Finnish (NFE)

AF:

0.0819

AC:

5572

AN:

68002

Other (OTH)

AF:

0.212

AC:

448

AN:

2114

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.500

Heterozygous variant carriers

1079

2158

3236

4315

5394

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:

0.137

Hom.:

678

Bravo

AF:

0.224

Asia WGS

AF:

0.322

AC:

1122

AN:

3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name

Calibrated prediction

Score

Prediction

BayesDel_noAF

Benign

-0.89

CADD

Benign

1.8

(source)

DANN

Benign

0.24

PhyloP100

-0.63

Mutation Taster

=294/6

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