Genetic Variant IRGM:n.*18A>G (chr5-150878054-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 ENST00000520549.1(IRGM):n.*18A>G variant causes a non coding transcript exon change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.161 in 460,854 control chromosomes in the GnomAD database, including 9,594 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 ( 5206 hom., cov: 32)

Exomes 𝑓: 0.14 ( 4388 hom. )

Consequence

IRGM
ENST00000520549.1 non_coding_transcript_exon

Scores

Clinical Significance

Not reported in ClinVar

Conservation

PhyloP100: 3.44

Publications

12 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:

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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=-0.65).

BA1

GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.439 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
IRGM	NR_170598.1 link	n.1721A>G		non_coding_transcript_exon_variant	Exon 3 of 5
IRGM	NM_001346557.2 link	c.532-1531A>G		intron_variant	Intron 2 of 3		NP_001333486.1	A1A4Y4-2

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
IRGM	ENST00000520549.1 link	n.*18A>G		non_coding_transcript_exon_variant	Exon 2 of 4	1		ENSP00000429819.1		A0A9H4B933
IRGM	ENST00000520549.1 link	n.*18A>G		3_prime_UTR_variant	Exon 2 of 4	1		ENSP00000429819.1		A0A9H4B933

Frequencies

GnomAD3 genomes

AF:

0.207

AC:

31384

AN:

151880

Hom.:

5192

Cov.:

show subpopulations

Gnomad AFR

AF:

0.444

Gnomad AMI

AF:

0.0351

Gnomad AMR

AF:

0.154

Gnomad ASJ

AF:

0.163

Gnomad EAS

AF:

0.427

Gnomad SAS

AF:

0.209

Gnomad FIN

AF:

0.0816

Gnomad MID

AF:

0.206

Gnomad NFE

AF:

0.0815

Gnomad OTH

AF:

0.211

GnomAD2 exomes

AF:

0.164

AC:

23737

AN:

144958

AF XY:

0.162

show subpopulations

Gnomad AFR exome

AF:

0.448

Gnomad AMR exome

AF:

0.142

Gnomad ASJ exome

AF:

0.173

Gnomad EAS exome

AF:

0.440

Gnomad FIN exome

AF:

0.0866

Gnomad NFE exome

AF:

0.0847

Gnomad OTH exome

AF:

0.160

GnomAD4 exome

AF:

0.138

AC:

42650

AN:

308856

Hom.:

4388

Cov.:

AF XY:

0.141

AC XY:

24877

AN XY:

175914

show subpopulations

African (AFR)

AF:

0.454

AC:

3901

AN:

8594

American (AMR)

AF:

0.142

AC:

3922

AN:

27642

Ashkenazi Jewish (ASJ)

AF:

0.174

AC:

1885

AN:

10860

East Asian (EAS)

AF:

0.431

AC:

3991

AN:

9270

South Asian (SAS)

AF:

0.194

AC:

11644

AN:

59954

European-Finnish (FIN)

AF:

0.0817

AC:

1171

AN:

14328

Middle Eastern (MID)

AF:

0.262

AC:

732

AN:

2790

European-Non Finnish (NFE)

AF:

0.0815

AC:

13122

AN:

160976

Other (OTH)

AF:

0.158

AC:

2282

AN:

14442

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.474

Heterozygous variant carriers

1565

3130

4695

6260

7825

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Exome Het

Exome Hom

Variant carriers

258

516

774

1032

1290

<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:

31438

AN:

151998

Hom.:

5206

Cov.:

AF XY:

0.206

AC XY:

15330

AN XY:

74324

show subpopulations

African (AFR)

AF:

0.444

AC:

18370

AN:

41370

American (AMR)

AF:

0.154

AC:

2349

AN:

15270

Ashkenazi Jewish (ASJ)

AF:

0.163

AC:

566

AN:

3466

East Asian (EAS)

AF:

0.427

AC:

2197

AN:

5140

South Asian (SAS)

AF:

0.208

AC:

1000

AN:

4816

European-Finnish (FIN)

AF:

0.0816

AC:

866

AN:

10610

Middle Eastern (MID)

AF:

0.211

AC:

AN:

294

European-Non Finnish (NFE)

AF:

0.0815

AC:

5546

AN:

68008

Other (OTH)

AF:

0.213

AC:

450

AN:

2112

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.501

Heterozygous variant carriers

1064

2128

3192

4256

5320

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Genome Het

Genome Hom

Variant carriers

304

608

912

1216

1520

<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:

0.124

Hom.:

2184

Bravo

AF:

0.226

Asia WGS

AF:

0.320

AC:

1114

AN:

3476

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

BayesDel_noAF

Benign

-0.65

CADD

Benign

(source)

DANN

Benign

0.25

PhyloP100

3.4

Splicing

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