dbSNP rs10058821: IRGM:c.-813A>G (chr5-150846823-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_001346557.2(IRGM):c.-813A>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 0.205 in 153,402 control chromosomes in the GnomAD database, including 5,234 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 ( 5225 hom., cov: 32)

Exomes 𝑓: 0.069 ( 9 hom. )

Consequence

IRGM
NM_001346557.2 5_prime_UTR

Scores

Clinical Significance

Not reported in ClinVar

Conservation

PhyloP100: -1.34

Publications

7 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=-0.91).

BA1

GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.436 is higher than 0.05.

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_001346557.2. 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.-813A>G	5_prime_UTR	Exon 1 of 2	NP_001139277.1
IRGM	NM_001346557.2		c.-813A>G	5_prime_UTR	Exon 1 of 4	NP_001333486.1
IRGM	NR_170598.1		n.303A>G	non_coding_transcript_exon	Exon 1 of 5

Ensembl Transcripts

Gene	Transcript	Tags	HGVSc	Effect	Exon Rank	Protein
IRGM	ENST00000522154.2	TSL:1 MANE Select	c.-813A>G	5_prime_UTR	Exon 1 of 2	ENSP00000428220.1
IRGM	ENST00000951736.1		c.-674A>G	5_prime_UTR	Exon 1 of 2	ENSP00000621795.1
IRGM	ENST00000609660.1	TSL:6	n.21A>G	non_coding_transcript_exon	Exon 1 of 1

Frequencies

GnomAD3 genomes

AF:

0.207

AC:

31369

AN:

151872

Hom.:

5211

Cov.:

show subpopulations

Gnomad AFR

AF:

0.442

Gnomad AMI

AF:

0.0352

Gnomad AMR

AF:

0.154

Gnomad ASJ

AF:

0.164

Gnomad EAS

AF:

0.433

Gnomad SAS

AF:

0.211

Gnomad FIN

AF:

0.0818

Gnomad MID

AF:

0.203

Gnomad NFE

AF:

0.0818

Gnomad OTH

AF:

0.211

GnomAD4 exome

AF:

0.0694

AC:

AN:

1412

Hom.:

Cov.:

AF XY:

0.0708

AC XY:

AN XY:

1074

show subpopulations

African (AFR)

AF:

0.292

AC:

AN:

American (AMR)

AF:

0.00

AC:

AN:

Ashkenazi Jewish (ASJ)

AF:

0.286

AC:

AN:

East Asian (EAS)

AF:

0.217

AC:

AN:

South Asian (SAS)

AF:

0.136

AC:

AN:

European-Finnish (FIN)

AF:

0.0357

AC:

AN:

Middle Eastern (MID)

AF:

0.00

AC:

AN:

European-Non Finnish (NFE)

AF:

0.0532

AC:

AN:

1184

Other (OTH)

AF:

0.109

AC:

AN:

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.476

Heterozygous variant carriers

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Exome Het

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:

31421

AN:

151990

Hom.:

5225

Cov.:

AF XY:

0.207

AC XY:

15365

AN XY:

74314

show subpopulations

African (AFR)

AF:

0.442

AC:

18276

AN:

41364

American (AMR)

AF:

0.154

AC:

2351

AN:

15288

Ashkenazi Jewish (ASJ)

AF:

0.164

AC:

570

AN:

3468

East Asian (EAS)

AF:

0.434

AC:

2240

AN:

5164

South Asian (SAS)

AF:

0.210

AC:

1009

AN:

4810

European-Finnish (FIN)

AF:

0.0818

AC:

866

AN:

10582

Middle Eastern (MID)

AF:

0.207

AC:

AN:

294

European-Non Finnish (NFE)

AF:

0.0819

AC:

5567

AN:

68000

Other (OTH)

AF:

0.213

AC:

449

AN:

2110

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.490

Heterozygous variant carriers

1035

2071

3106

4142

5177

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

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name

Calibrated prediction

Score

Prediction

BayesDel_noAF

Benign

-0.91

CADD

Benign

2.1

(source)

DANN

Benign

0.17

PhyloP100

-1.3

PromoterAI

0.16

Neutral

(source)

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