Genetic Variant IRGM:c.-942delG (chr5-150846690-CG-C) – ACMG Classification: Benign (-8 pts)

Variant summary

Our verdict is Benign. The variant received -8 ACMG points: 0P and 8B. BA1

The NM_001145805.2(IRGM):c.-942delG variant causes a 5 prime UTR change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.206 in 152,114 control chromosomes in the GnomAD database, including 5,179 homozygotes. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar.

Frequency

Genomes: 𝑓 0.21 ( 5179 hom., cov: 28)

Exomes 𝑓: 0.037 ( 0 hom. )

Consequence

IRGM
NM_001145805.2 5_prime_UTR

Scores

Not classified

Clinical Significance

Not reported in ClinVar

Conservation

PhyloP100: 0.00

Publications

5 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 -8 ACMG points.

BA1

GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.435 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.-942delG	5_prime_UTR	Exon 1 of 2	NP_001139277.1	A1A4Y4-1
IRGM	NM_001346557.2		c.-942delG	5_prime_UTR	Exon 1 of 4	NP_001333486.1	A1A4Y4-2
IRGM	NR_170598.1		n.174delG	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.-942delG	5_prime_UTR	Exon 1 of 2	ENSP00000428220.1	A1A4Y4-1
IRGM	ENST00000951736.1		c.-803delG	5_prime_UTR	Exon 1 of 2	ENSP00000621795.1
IRGM	ENST00000609660.1	TSL:6	n.-112delG	upstream_gene	N/A

Frequencies

GnomAD3 genomes

AF:

0.206

AC:

31199

AN:

151650

Hom.:

5165

Cov.:

show subpopulations

Gnomad AFR

AF:

0.441

Gnomad AMI

AF:

0.0341

Gnomad AMR

AF:

0.154

Gnomad ASJ

AF:

0.164

Gnomad EAS

AF:

0.431

Gnomad SAS

AF:

0.210

Gnomad FIN

AF:

0.0809

Gnomad MID

AF:

0.203

Gnomad NFE

AF:

0.0815

Gnomad OTH

AF:

0.209

GnomAD4 exome

AF:

0.0374

AC:

AN:

348

Hom.:

Cov.:

AF XY:

0.0338

AC XY:

AN XY:

266

show subpopulations

African (AFR)

AF:

0.250

AC:

AN:

American (AMR)

AC:

AN:

Ashkenazi Jewish (ASJ)

AF:

0.250

AC:

AN:

East Asian (EAS)

AF:

0.0625

AC:

AN:

South Asian (SAS)

AF:

0.00

AC:

AN:

European-Finnish (FIN)

AF:

0.00

AC:

AN:

Middle Eastern (MID)

AF:

0.500

AC:

AN:

European-Non Finnish (NFE)

AF:

0.0270

AC:

AN:

296

Other (OTH)

AF:

0.00

AC:

AN:

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.521

Heterozygous variant carriers

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

GnomAD4 genome

AF:

0.206

AC:

31250

AN:

151766

Hom.:

5179

Cov.:

AF XY:

0.206

AC XY:

15287

AN XY:

74208

show subpopulations

African (AFR)

AF:

0.441

AC:

18186

AN:

41266

American (AMR)

AF:

0.153

AC:

2343

AN:

15266

Ashkenazi Jewish (ASJ)

AF:

0.164

AC:

568

AN:

3464

East Asian (EAS)

AF:

0.432

AC:

2219

AN:

5136

South Asian (SAS)

AF:

0.209

AC:

1002

AN:

4802

European-Finnish (FIN)

AF:

0.0809

AC:

855

AN:

10574

Middle Eastern (MID)

AF:

0.207

AC:

AN:

294

European-Non Finnish (NFE)

AF:

0.0816

AC:

5542

AN:

67950

Other (OTH)

AF:

0.210

AC:

443

AN:

2106

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.483

Heterozygous variant carriers

970

1940

2910

3880

4850

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Genome Het

Genome Hom

Variant carriers

300

600

900

1200

1500

<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:

0.0196

Hom.:

Asia WGS

AF:

0.321

AC:

1116

AN:

3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name

Calibrated prediction

Score

Prediction

PhyloP100

0.0

Mutation Taster

=298/2

polymorphism (auto)

(source)

Splicing

Name

Calibrated prediction

Score

Prediction

SpliceAI score (max)

0.020

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

ClinVar

Computational scores

Splicing

Publications

Other links and lift over