dbSNP rs34156253: IRGM:c.-968A>G (chr5-150846668-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_001145805.2(IRGM):c.-968A>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 0.206 in 151,786 control chromosomes in the GnomAD database, including 5,184 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 ( 5183 hom., cov: 32)

Exomes 𝑓: 0.047 ( 1 hom. )

Consequence

IRGM
NM_001145805.2 5_prime_UTR

Scores

Clinical Significance

Not reported in ClinVar

Conservation

PhyloP100: -1.34

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:

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=-0.98).

BA1

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

Transcripts

RefSeq

Gene	Transcript	HGVSc	Effect	Exon rank	MANE	Protein	UniProt
IRGM	NM_001145805.2 link	c.-968A>G	5_prime_UTR_variant	Exon 1 of 2	ENST00000522154.2	NP_001139277.1	A1A4Y4-1
IRGM	NR_170598.1 link	n.148A>G	non_coding_transcript_exon_variant	Exon 1 of 5
IRGM	NM_001346557.2 link	c.-968A>G	5_prime_UTR_variant	Exon 1 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.-968A>G		5_prime_UTR_variant	Exon 1 of 2	1	NM_001145805.2	ENSP00000428220.1		A1A4Y4-1
IRGM	ENST00000609660.1 link	n.-135A>G		upstream_gene_variant		6

Frequencies

GnomAD3 genomes

AF:

0.206

AC:

31129

AN:

151430

Hom.:

5169

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:

0.432

Gnomad SAS

AF:

0.207

Gnomad FIN

AF:

0.0809

Gnomad MID

AF:

0.201

Gnomad NFE

AF:

0.0812

Gnomad OTH

AF:

0.209

GnomAD4 exome

AF:

0.0466

AC:

AN:

236

Hom.:

Cov.:

AF XY:

0.0484

AC XY:

AN XY:

186

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:

0.200

AC:

AN:

South Asian (SAS)

AF:

0.00

AC:

AN:

European-Finnish (FIN)

AF:

0.00

AC:

AN:

Middle Eastern (MID)

AC:

AN:

European-Non Finnish (NFE)

AF:

0.0300

AC:

AN:

200

Other (OTH)

AF:

0.00

AC:

AN:

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.519

Heterozygous variant carriers

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

GnomAD4 genome

AF:

0.206

AC:

31182

AN:

151550

Hom.:

5183

Cov.:

AF XY:

0.206

AC XY:

15255

AN XY:

74062

show subpopulations

African (AFR)

AF:

0.441

AC:

18175

AN:

41216

American (AMR)

AF:

0.153

AC:

2333

AN:

15236

Ashkenazi Jewish (ASJ)

AF:

0.164

AC:

568

AN:

3464

East Asian (EAS)

AF:

0.433

AC:

2222

AN:

5130

South Asian (SAS)

AF:

0.206

AC:

982

AN:

4760

European-Finnish (FIN)

AF:

0.0809

AC:

854

AN:

10554

Middle Eastern (MID)

AF:

0.205

AC:

AN:

292

European-Non Finnish (NFE)

AF:

0.0812

AC:

5516

AN:

67896

Other (OTH)

AF:

0.211

AC:

441

AN:

2094

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.484

Heterozygous variant carriers

949

1897

2846

3794

4743

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Alfa

AF:

0.148

Hom.:

308

Asia WGS

AF:

0.321

AC:

1118

AN:

3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

BayesDel_noAF

Benign

-0.98

CADD

Benign

3.4

(source)

DANN

Benign

0.13

PhyloP100

-1.3

PromoterAI

0.016

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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rs34156253

Variant summary

Frequency

Consequence

Scores

Clinical Significance

Conservation

Publications

ACMG classification

Transcripts

RefSeq

Ensembl

Frequencies

Age Distribution

ClinVar

Computational scores

Splicing

Publications

Other links and lift over