Genetic Variant IRGM:c.-311_-304dupGTTTGTTT (chr5-150847809-T-TTTTGTTTG) – ACMG Classification: Benign (-8 pts)

Variant summary

Our verdict is Benign. The variant received -8 ACMG points: 0P and 8B. BA1

The NM_001145805.2(IRGM):c.-311_-304dupGTTTGTTT variant causes a 5 prime UTR change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0287 in 276,690 control chromosomes in the GnomAD database, including 599 homozygotes. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar.

Frequency

Genomes: 𝑓 0.047 ( 553 hom., cov: 26)

Exomes 𝑓: 0.0065 ( 46 hom. )

Consequence

IRGM
NM_001145805.2 5_prime_UTR

Scores

Not classified

Clinical Significance

Not reported in ClinVar

Conservation

PhyloP100: 0.876

Publications

3 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 -8 ACMG points.

BA1

GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.161 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	Effect	Exon rank	MANE	Protein	UniProt
IRGM	NM_001145805.2 link	c.-311_-304dupGTTTGTTT	5_prime_UTR_variant	Exon 2 of 2	ENST00000522154.2	NP_001139277.1	A1A4Y4-1
IRGM	NR_170598.1 link	n.805_812dupGTTTGTTT	non_coding_transcript_exon_variant	Exon 2 of 5
IRGM	NM_001346557.2 link	c.-311_-304dupGTTTGTTT	5_prime_UTR_variant	Exon 2 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.-311_-304dupGTTTGTTT		5_prime_UTR_variant	Exon 2 of 2	1	NM_001145805.2	ENSP00000428220.1		A1A4Y4-1

Frequencies

GnomAD3 genomes

AF:

0.0468

AC:

7090

AN:

151486

Hom.:

542

Cov.:

show subpopulations

Gnomad AFR

AF:

0.163

Gnomad AMI

AF:

0.00

Gnomad AMR

AF:

0.0139

Gnomad ASJ

AF:

0.00

Gnomad EAS

AF:

0.00234

Gnomad SAS

AF:

0.00563

Gnomad FIN

AF:

0.0000949

Gnomad MID

AF:

0.00318

Gnomad NFE

AF:

0.000721

Gnomad OTH

AF:

0.0369

GnomAD4 exome

AF:

0.00650

AC:

813

AN:

125086

Hom.:

Cov.:

AF XY:

0.00593

AC XY:

389

AN XY:

65554

show subpopulations

African (AFR)

AF:

0.149

AC:

596

AN:

4012

American (AMR)

AF:

0.0104

AC:

AN:

5012

Ashkenazi Jewish (ASJ)

AF:

0.00

AC:

AN:

3482

East Asian (EAS)

AF:

0.00215

AC:

AN:

6502

South Asian (SAS)

AF:

0.00251

AC:

AN:

15128

European-Finnish (FIN)

AF:

0.00

AC:

AN:

5344

Middle Eastern (MID)

AF:

0.00622

AC:

AN:

482

European-Non Finnish (NFE)

AF:

0.000536

AC:

AN:

78336

Other (OTH)

AF:

0.0100

AC:

AN:

6788

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.500

Heterozygous variant carriers

106

141

176

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Exome Het

Exome Hom

Variant carriers

100

<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:

0.0471

AC:

7137

AN:

151604

Hom.:

553

Cov.:

AF XY:

0.0456

AC XY:

3376

AN XY:

74038

show subpopulations

African (AFR)

AF:

0.164

AC:

6756

AN:

41214

American (AMR)

AF:

0.0138

AC:

211

AN:

15246

Ashkenazi Jewish (ASJ)

AF:

0.00

AC:

AN:

3468

East Asian (EAS)

AF:

0.00235

AC:

AN:

5114

South Asian (SAS)

AF:

0.00585

AC:

AN:

4790

European-Finnish (FIN)

AF:

0.0000949

AC:

AN:

10532

Middle Eastern (MID)

AF:

0.00342

AC:

AN:

292

European-Non Finnish (NFE)

AF:

0.000721

AC:

AN:

67932

Other (OTH)

AF:

0.0375

AC:

AN:

2106

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.503

Heterozygous variant carriers

294

587

881

1174

1468

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Genome Het

Genome Hom

Variant carriers

140

210

280

350

<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:

0.00

Hom.:

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

PhyloP100

0.88

Mutation Taster

=297/3

polymorphism (auto)

(source)

Splicing

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

Publications

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5-150847809-TTTTG-TTTTGTTTGTTTG

Variant summary

Frequency

Consequence

Scores

Clinical Significance

Conservation

Publications

ACMG classification

Transcripts

RefSeq

Ensembl

Frequencies

Age Distribution

Age Distribution

ClinVar

Computational scores

Splicing

Publications

Other links and lift over