dbSNP rs4958847: IRGM:n.156+11371G>A (chr5-150860025-G-A) – ACMG Classification: Benign (-12 pts)

Germline classification Cancer classification (beta)

Variant summary

Our verdict is . The variant received -12 ACMG points: 0P and 12B. BA1BP4_Strong

The NM_001346557.2(IRGM):c.531+11371G>A variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a cumulative frequency of 0.249 (AC=37,862) in the gnomAD database across 151,964 control chromosomes, including 6,791 homozygotes. The grpmax filtering allele frequency (95% CI) is 0.596. In-silico predictor (BayesDel (noAF)) classifies this variant as likely benign. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar.

Frequency

Genomes: 𝑓 0.25 ( 6791 hom., cov: 32)

Consequence

IRGM
NM_001346557.2 intron

Scores

Clinical Significance

Not reported in ClinVar

Conservation

PhyloP100: -0.786

Publications

93 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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new If you want to explore the variant's impact on the transcript NM_001346557.2, check out the Mutation Effect Viewer. This is especially useful for frameshift variants or if you want to visualize the effect of exon loss / intron retention.

Classification according to ACMG Germline Pathogenicity v2019

Classification was made for transcript

Our verdict: Benign. The variant received -12 ACMG points.

BP4

Computational evidence supports benign — no pathogenic computational or splicing signal (BP4); No splicing predictor data available.; Germline computational verdict: benign (Strong).

BA1

GnomAD effective popmax AF >5% — BA1 stand-alone benign; GnomAD reliable popmax AF = 0.5962 — exceeds 5%% threshold (BA1 applied)

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_001346557.2. You can select a different transcript below to see updated ACMG assignments.

RefSeq Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	IRGM	NM_001346557.2		c.531+11371G>A		intron	N/A	NP_001333486.1	A1A4Y4-2
	IRGM	NR_170598.1		n.1646+11371G>A		intron	N/A

Ensembl Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	IRGM	ENST00000520549.1	TSL:1	n.156+11371G>A		intron	N/A	ENSP00000429819.1	A0A9H4B933

Frequencies

GnomAD3 genomes

AF:

0.249

AC:

37803

AN:

151846

Hom.:

6772

Cov.:

show subpopulations

Gnomad AFR

AF:

0.468

Gnomad AMI

AF:

0.159

Gnomad AMR

AF:

0.186

Gnomad ASJ

AF:

0.200

Gnomad EAS

AF:

0.614

Gnomad SAS

AF:

0.274

Gnomad FIN

AF:

0.114

Gnomad MID

AF:

0.315

Gnomad NFE

AF:

0.124

Gnomad OTH

AF:

0.251

We have no GnomAD4 exomes data on this position. Probably position not covered by the project.

GnomAD4 genome

AF:

0.249

AC:

37862

AN:

151964

Hom.:

6791

Cov.:

AF XY:

0.250

AC XY:

18601

AN XY:

74286

show subpopulations

African (AFR)

AF:

0.468

AC:

19411

AN:

41436

American (AMR)

AF:

0.186

AC:

2841

AN:

15270

Ashkenazi Jewish (ASJ)

AF:

0.200

AC:

694

AN:

3464

East Asian (EAS)

AF:

0.614

AC:

3171

AN:

5164

South Asian (SAS)

AF:

0.273

AC:

1312

AN:

4808

European-Finnish (FIN)

AF:

0.114

AC:

1206

AN:

10568

Middle Eastern (MID)

AF:

0.315

AC:

AN:

292

European-Non Finnish (NFE)

AF:

0.125

AC:

8460

AN:

67946

Other (OTH)

AF:

0.252

AC:

530

AN:

2106

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.501

Heterozygous variant carriers

1250

2500

3749

4999

6249

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Genome Het

Genome Hom

Variant carriers

366

732

1098

1464

1830

<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:

0.174

Hom.:

1852

Bravo

AF:

0.267

Asia WGS

AF:

0.415

AC:

1443

AN:

3478

Local populations

ToMMo 61KJPN (+60KJPN MNV)

AF:

0.488

AC:

59830

AN:

122674

Turkish Variome

AF:

0.226

AC:

349

AN:

1546

Hom.:

WBBC (Westlake BioBank for Chinese) pilot

AF:

0.619

AC:

5550

AN:

8960

Hom.:

1721

ABraOM SABE-WGS-1171

AF:

0.228

AC:

535

AN:

2342

Hom.:

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name

Calibrated prediction

Score

Prediction

BayesDel_noAF

Benign

-0.93

CADD

Benign

0.66

(source)

DANN

Benign

0.63

PhyloP100

-0.79

Splicing

Find out detailed SpliceAI scores and Pangolin per-transcript scores at spliceailookup.broadinstitute.org

MaxEntScan Visualizer can be used to analyze the impact of this mutation on the neighboring sequence.

Publications

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Variant summary

Frequency

Consequence

Scores

Clinical Significance

Conservation

Publications

Classification according to ACMG Germline Pathogenicity v2019

Variant Effect in Transcripts

RefSeq Transcripts

Ensembl Transcripts

Frequencies

Age Distribution

Local populations

ClinVar

Computational scores

Splicing

Publications

Other links and lift over