dbSNP rs9637870: IRGM:c.-71G>A (chr5-150848053-G-A) – 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.-71G>A variant causes a 5 prime UTR change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.114 in 1,231,878 control chromosomes in the GnomAD database, including 12,014 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 0.17 ( 2928 hom., cov: 32)

Exomes 𝑓: 0.11 ( 9086 hom. )

Consequence

IRGM
NM_001145805.2 5_prime_UTR

Scores

Clinical Significance

Not reported in ClinVar

Conservation

PhyloP100: -0.104

Publications

11 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=-1.02).

BA1

GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.418 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	Effect	Exon rank	MANE	Protein	UniProt
IRGM	NM_001145805.2 link	c.-71G>A	5_prime_UTR_variant	Exon 2 of 2	ENST00000522154.2	NP_001139277.1	A1A4Y4-1
IRGM	NR_170598.1 link	n.1045G>A	non_coding_transcript_exon_variant	Exon 2 of 5
IRGM	NM_001346557.2 link	c.-71G>A	5_prime_UTR_variant	Exon 2 of 4		NP_001333486.1	A1A4Y4-2

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
IRGM	ENST00000522154.2 link	c.-71G>A		5_prime_UTR_variant	Exon 2 of 2	1	NM_001145805.2	ENSP00000428220.1		A1A4Y4-1

Frequencies

GnomAD3 genomes

AF:

0.165

AC:

25087

AN:

151918

Hom.:

2930

Cov.:

show subpopulations

Gnomad AFR

AF:

0.296

Gnomad AMI

AF:

0.0351

Gnomad AMR

AF:

0.143

Gnomad ASJ

AF:

0.164

Gnomad EAS

AF:

0.432

Gnomad SAS

AF:

0.207

Gnomad FIN

AF:

0.0825

Gnomad MID

AF:

0.203

Gnomad NFE

AF:

0.0815

Gnomad OTH

AF:

0.178

GnomAD4 exome

AF:

0.107

AC:

115142

AN:

1079842

Hom.:

9086

Cov.:

AF XY:

0.109

AC XY:

58140

AN XY:

533932

show subpopulations

African (AFR)

AF:

0.305

AC:

7379

AN:

24200

American (AMR)

AF:

0.135

AC:

3090

AN:

22822

Ashkenazi Jewish (ASJ)

AF:

0.170

AC:

3086

AN:

18118

East Asian (EAS)

AF:

0.388

AC:

13191

AN:

34002

South Asian (SAS)

AF:

0.197

AC:

11723

AN:

59520

European-Finnish (FIN)

AF:

0.0829

AC:

3770

AN:

45494

Middle Eastern (MID)

AF:

0.226

AC:

1005

AN:

4444

European-Non Finnish (NFE)

AF:

0.0792

AC:

65349

AN:

824808

Other (OTH)

AF:

0.141

AC:

6549

AN:

46434

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.506

Heterozygous variant carriers

5042

10084

15126

20168

25210

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Exome Het

Exome Hom

Variant carriers

2552

5104

7656

10208

12760

<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:

0.165

AC:

25103

AN:

152036

Hom.:

2928

Cov.:

AF XY:

0.166

AC XY:

12354

AN XY:

74326

show subpopulations

African (AFR)

AF:

0.296

AC:

12248

AN:

41416

American (AMR)

AF:

0.142

AC:

2176

AN:

15276

Ashkenazi Jewish (ASJ)

AF:

0.164

AC:

568

AN:

3468

East Asian (EAS)

AF:

0.433

AC:

2238

AN:

5166

South Asian (SAS)

AF:

0.205

AC:

989

AN:

4814

European-Finnish (FIN)

AF:

0.0825

AC:

874

AN:

10592

Middle Eastern (MID)

AF:

0.207

AC:

AN:

294

European-Non Finnish (NFE)

AF:

0.0815

AC:

5540

AN:

67990

Other (OTH)

AF:

0.179

AC:

377

AN:

2108

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.502

Heterozygous variant carriers

1000

2000

2999

3999

4999

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Genome Het

Genome Hom

Variant carriers

264

528

792

1056

1320

<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:

0.0323

Hom.:

Bravo

AF:

0.177

Asia WGS

AF:

0.301

AC:

1047

AN:

3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

BayesDel_noAF

Benign

-1.0

CADD

Benign

4.5

(source)

DANN

Benign

0.40

PhyloP100

-0.10

Mutation Taster

=300/0

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

Transcripts

RefSeq

Ensembl

Frequencies

Age Distribution

Age Distribution

ClinVar

Computational scores

Splicing

Publications

Other links and lift over