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. Variant has been reported in ClinVar as (no stars).

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:

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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=-1.02).

BA1

GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.418 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.-71G>A	5_prime_UTR	Exon 2 of 2	NP_001139277.1	A1A4Y4-1
IRGM	NM_001346557.2		c.-71G>A	5_prime_UTR	Exon 2 of 4	NP_001333486.1	A1A4Y4-2
IRGM	NR_170598.1		n.1045G>A	non_coding_transcript_exon	Exon 2 of 5

Ensembl Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	IRGM	ENST00000522154.2	TSL:1 MANE Select	c.-71G>A		5_prime_UTR	Exon 2 of 2	ENSP00000428220.1	A1A4Y4-1
	IRGM	ENST00000951736.1		c.-71G>A		5_prime_UTR	Exon 2 of 2	ENSP00000621795.1

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 v4.9

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

Variant Effect in Transcripts

RefSeq Transcripts

Ensembl Transcripts

Frequencies

Age Distribution

Age Distribution

ClinVar

Computational scores

Splicing

Publications

Other links and lift over