Genetic Variant IRGM:n.156+121T>C (chr5-150848775-T-C) – ACMG Classification: Likely_benign (-4 pts)

Variant summary

Our verdict is Likely benign. The variant received -4 ACMG points: 0P and 4B. BP4_Strong

The NM_001346557.2(IRGM):c.531+121T>C variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.000404 in 792,484 control chromosomes in the GnomAD database, including 1 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 0.0014 ( 1 hom., cov: 32)

Exomes 𝑓: 0.00016 ( 0 hom. )

Consequence

IRGM
NM_001346557.2 intron

Scores

Clinical Significance

Not reported in ClinVar

Conservation

PhyloP100: 0.447

Publications

0 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: Likely_benign. The variant received -4 ACMG points.

BP4

Computational evidence support a benign effect (BayesDel_noAF=-0.95).

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

Gene	Transcript	Tags	HGVSc	Effect	Exon Rank	Protein	UniProt
IRGM	NM_001346557.2		c.531+121T>C	intron	N/A	NP_001333486.1	A1A4Y4-2
IRGM	NR_170598.1		n.1646+121T>C	intron	N/A
IRGM	NM_001145805.2	MANE Select	c.*106T>C	downstream_gene	N/A	NP_001139277.1	A1A4Y4-1

Ensembl Transcripts

Gene	Transcript	Tags	HGVSc	Effect	Exon Rank	Protein	UniProt
IRGM	ENST00000520549.1	TSL:1	n.156+121T>C	intron	N/A	ENSP00000429819.1	A0A9H4B933
IRGM	ENST00000522154.2	TSL:1 MANE Select	c.*106T>C	downstream_gene	N/A	ENSP00000428220.1	A1A4Y4-1
IRGM	ENST00000951736.1		c.*106T>C	downstream_gene	N/A	ENSP00000621795.1

Frequencies

GnomAD3 genomes

AF:

0.00143

AC:

218

AN:

152134

Hom.:

Cov.:

show subpopulations

Gnomad AFR

AF:

0.00422

Gnomad AMI

AF:

0.00

Gnomad AMR

AF:

0.00236

Gnomad ASJ

AF:

0.00

Gnomad EAS

AF:

0.00

Gnomad SAS

AF:

0.00

Gnomad FIN

AF:

0.00

Gnomad MID

AF:

0.00

Gnomad NFE

AF:

0.00

Gnomad OTH

AF:

0.00334

GnomAD4 exome

AF:

0.000159

AC:

102

AN:

640232

Hom.:

AF XY:

0.000119

AC XY:

AN XY:

326874

show subpopulations

African (AFR)

AF:

0.00426

AC:

AN:

15742

American (AMR)

AF:

0.000889

AC:

AN:

19122

Ashkenazi Jewish (ASJ)

AF:

0.00

AC:

AN:

14874

East Asian (EAS)

AF:

0.00

AC:

AN:

31974

South Asian (SAS)

AF:

0.00

AC:

AN:

48430

European-Finnish (FIN)

AF:

0.00

AC:

AN:

43778

Middle Eastern (MID)

AF:

0.00

AC:

AN:

2378

European-Non Finnish (NFE)

AF:

0.0000116

AC:

AN:

432026

Other (OTH)

AF:

0.000407

AC:

AN:

31908

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.500

Heterozygous variant carriers

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Exome Het

Variant carriers

<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:

0.00143

AC:

218

AN:

152252

Hom.:

Cov.:

AF XY:

0.00118

AC XY:

AN XY:

74454

show subpopulations

African (AFR)

AF:

0.00421

AC:

175

AN:

41552

American (AMR)

AF:

0.00235

AC:

AN:

15290

Ashkenazi Jewish (ASJ)

AF:

0.00

AC:

AN:

3468

East Asian (EAS)

AF:

0.00

AC:

AN:

5174

South Asian (SAS)

AF:

0.00

AC:

AN:

4814

European-Finnish (FIN)

AF:

0.00

AC:

AN:

10616

Middle Eastern (MID)

AF:

0.00

AC:

AN:

294

European-Non Finnish (NFE)

AF:

0.00

AC:

AN:

68016

Other (OTH)

AF:

0.00331

AC:

AN:

2116

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.505

Heterozygous variant carriers

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Genome Het

Genome Hom

Variant carriers

<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:

0.000971

Hom.:

Bravo

AF:

0.00198

Asia WGS

AF:

0.000289

AC:

AN:

3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name

Calibrated prediction

Score

Prediction

BayesDel_noAF

Benign

-0.95

CADD

Benign

6.3

(source)

DANN

Benign

0.52

PhyloP100

0.45

Splicing

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