Variant NM_001145805.2:c.313C>T details in Genebe, Genetics Data Aggregator

Variant summary

Our verdict is Benign. Variant got -13 ACMG points: 0P and 13B. BP4_StrongBP7BA1

The NM_001145805.2(IRGM):c.313C>T(p.Leu105Leu) variant causes a synonymous change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.119 in 1,551,610 control chromosomes in the GnomAD database, including 18,592 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★★).

Frequency

Genomes: 𝑓 0.21 ( 5257 hom., cov: 32)

Exomes 𝑓: 0.11 ( 13335 hom. )

Consequence

IRGM
NM_001145805.2 synonymous

Scores

Clinical Significance

Benign criteria provided, multiple submitters, no conflicts P:1B:2

Conservation

PhyloP100: 0.655

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 made for transcript

Verdict is Benign. Variant got -13 ACMG points.

BP4

Computational evidence support a benign effect (BayesDel_noAF=-0.86).

BP7

Synonymous conserved (PhyloP=0.655 with no splicing effect.

BA1

GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.437 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
IRGM	NM_001145805.2 link	c.313C>T	p.Leu105Leu	synonymous_variant	Exon 2 of 2	ENST00000522154.2	NP_001139277.1	A1A4Y4-1
IRGM	NM_001346557.2 link	c.313C>T	p.Leu105Leu	synonymous_variant	Exon 2 of 4		NP_001333486.1	A1A4Y4-2
IRGM	NR_170598.1 link	n.1428C>T		non_coding_transcript_exon_variant	Exon 2 of 5

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
IRGM	ENST00000522154.2 link	c.313C>T	p.Leu105Leu	synonymous_variant	Exon 2 of 2	1	NM_001145805.2	ENSP00000428220.1		A1A4Y4-1

Frequencies

GnomAD3 genomes

AF:

0.207

AC:

31482

AN:

152052

Hom.:

5243

Cov.:

show subpopulations

Gnomad AFR

AF:

0.443

Gnomad AMI

AF:

0.0351

Gnomad AMR

AF:

0.155

Gnomad ASJ

AF:

0.164

Gnomad EAS

AF:

0.433

Gnomad SAS

AF:

0.212

Gnomad FIN

AF:

0.0821

Gnomad MID

AF:

0.206

Gnomad NFE

AF:

0.0819

Gnomad OTH

AF:

0.211

GnomAD3 exomes

AF:

0.165

AC:

25447

AN:

154216

Hom.:

3159

AF XY:

0.164

AC XY:

13452

AN XY:

81810

show subpopulations

Gnomad AFR exome

AF:

0.455

Gnomad AMR exome

AF:

0.143

Gnomad ASJ exome

AF:

0.175

Gnomad EAS exome

AF:

0.440

Gnomad SAS exome

AF:

0.204

Gnomad FIN exome

AF:

0.0816

Gnomad NFE exome

AF:

0.0900

Gnomad OTH exome

AF:

0.161

GnomAD4 exome

AF:

0.109

AC:

153155

AN:

1399440

Hom.:

13335

Cov.:

AF XY:

0.111

AC XY:

76783

AN XY:

690246

show subpopulations

Gnomad4 AFR exome

AF:

0.454

Gnomad4 AMR exome

AF:

0.144

Gnomad4 ASJ exome

AF:

0.170

Gnomad4 EAS exome

AF:

0.389

Gnomad4 SAS exome

AF:

0.200

Gnomad4 FIN exome

AF:

0.0839

Gnomad4 NFE exome

AF:

0.0790

Gnomad4 OTH exome

AF:

0.153

GnomAD4 genome

AF:

0.207

AC:

31535

AN:

152170

Hom.:

5257

Cov.:

AF XY:

0.207

AC XY:

15406

AN XY:

74394

show subpopulations

Gnomad4 AFR

AF:

0.443

Gnomad4 AMR

AF:

0.154

Gnomad4 ASJ

AF:

0.164

Gnomad4 EAS

AF:

0.434

Gnomad4 SAS

AF:

0.211

Gnomad4 FIN

AF:

0.0821

Gnomad4 NFE

AF:

0.0819

Gnomad4 OTH

AF:

0.212

Alfa

AF:

0.141

Hom.:

1508

Bravo

AF:

0.224

Asia WGS

AF:

0.323

AC:

1123

AN:

3478

ClinVar

Significance: Benign

Submissions summary: Pathogenic:1Benign:2

Revision: criteria provided, multiple submitters, no conflicts

LINK: link

Submissions by phenotype

Inflammatory bowel disease 19

Pathogenic:1Benign:1

Apr 04, 2024

Genomic Medicine Center of Excellence, King Faisal Specialist Hospital and Research Centre

Significance: Benign

Review Status: criteria provided, single submitter

Collection Method: clinical testing

- -

Mar 01, 2011

OMIM

Significance: Pathogenic

Review Status: no assertion criteria provided

Collection Method: literature only

- -

not specified

Benign:1

Oct 28, 2020

H3Africa Consortium

Significance: Benign

Review Status: criteria provided, single submitter

Collection Method: research

While the frequency of the alternate allele in gnoMAD v2.0.2 is 0.646, its frequency in African populations is >5%. This suggests that previous classifications of this variant as pathogenic are in error. -

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

BayesDel_noAF

Benign

-0.86

CADD

Benign

0.53

DANN

Benign

0.53

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

LitVar

Below is the list of publications found by LitVar. It may be empty.

Variant summary

Frequency

Consequence

Scores

Clinical Significance

Conservation

ACMG classification

Transcripts

RefSeq

Ensembl

Frequencies

ClinVar

Submissions by phenotype

Computational scores

Splicing

Publications

LitVar

Other links and lift over