Genetic Variant NM_000884.3:c.1006+202C>T (chr3-49026122-G-A) – ACMG Classification: Benign (-10 pts)

Variant summary

Our verdict is Benign. The variant received -10 ACMG points: 0P and 10B. BP4_ModerateBS1BS2

The NM_000884.3(IMPDH2):c.1006+202C>T variant causes a intron change. The variant allele was found at a frequency of 0.0116 in 681,816 control chromosomes in the GnomAD database, including 92 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 0.0087 ( 6 hom., cov: 33)

Exomes 𝑓: 0.012 ( 86 hom. )

Consequence

IMPDH2
NM_000884.3 intron

Scores

Clinical Significance

Not reported in ClinVar

Conservation

PhyloP100: 5.95

Publications

0 publications found

Variant links:

Genes affected

IMPDH2 (HGNC:6053): (inosine monophosphate dehydrogenase 2) This gene encodes the rate-limiting enzyme in the de novo guanine nucleotide biosynthesis. It is thus involved in maintaining cellular guanine deoxy- and ribonucleotide pools needed for DNA and RNA synthesis. The encoded protein catalyzes the NAD-dependent oxidation of inosine-5'-monophosphate into xanthine-5'-monophosphate, which is then converted into guanosine-5'-monophosphate. This gene is up-regulated in some neoplasms, suggesting it may play a role in malignant transformation. [provided by RefSeq, Jul 2008]

IMPDH2 links:

ENSG00000290315 (HGNC:):

ENSG00000290315 links:

Genome browser will be placed here

ACMG classification

Classification was made for transcript

Our verdict: Benign. The variant received -10 ACMG points.

BP4

Computational evidence support a benign effect (BayesDel_noAF=-0.22).

BS1

Variant frequency is greater than expected in population sas. GnomAd4 allele frequency = 0.00873 (1330/152346) while in subpopulation SAS AF = 0.0228 (110/4828). AF 95% confidence interval is 0.0193. There are 6 homozygotes in GnomAd4. There are 682 alleles in the male GnomAd4 subpopulation. Median coverage is 33. This position passed quality control check.

BS2

High AC in GnomAd4 at 1330 AD gene.

Transcripts

RefSeq

Gene	Transcript	HGVSc	Effect	Exon rank	MANE	Protein	UniProt
IMPDH2	NM_000884.3 link	c.1006+202C>T	intron_variant	Intron 9 of 13	ENST00000326739.9	NP_000875.2	P12268A0A384N6C2
IMPDH2	NM_001410759.1 link	c.1007-56C>T	intron_variant	Intron 9 of 14		NP_001397688.1
IMPDH2	NM_001410760.1 link	c.932-56C>T	intron_variant	Intron 8 of 13		NP_001397689.1
IMPDH2	NM_001410761.1 link	c.931+202C>T	intron_variant	Intron 8 of 12		NP_001397690.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
IMPDH2	ENST00000326739.9 link	c.1006+202C>T		intron_variant	Intron 9 of 13	1	NM_000884.3	ENSP00000321584.4		P12268
ENSG00000290315	ENST00000703936.1 link	c.3046+202C>T		intron_variant	Intron 17 of 21			ENSP00000515567.1		A0A994J749

Frequencies

GnomAD3 genomes

AF:

0.00872

AC:

1328

AN:

152228

Hom.:

Cov.:

show subpopulations

Gnomad AFR

AF:

0.00203

Gnomad AMI

AF:

0.0219

Gnomad AMR

AF:

0.00739

Gnomad ASJ

AF:

0.0170

Gnomad EAS

AF:

0.00

Gnomad SAS

AF:

0.0224

Gnomad FIN

AF:

0.0160

Gnomad MID

AF:

0.0253

Gnomad NFE

AF:

0.0108

Gnomad OTH

AF:

0.0139

GnomAD4 exome

AF:

0.0124

AC:

6581

AN:

529470

Hom.:

Cov.:

AF XY:

0.0136

AC XY:

3916

AN XY:

287094

show subpopulations

African (AFR)

AF:

0.00123

AC:

AN:

15432

American (AMR)

AF:

0.00702

AC:

238

AN:

33908

Ashkenazi Jewish (ASJ)

AF:

0.0196

AC:

379

AN:

19376

East Asian (EAS)

AF:

0.0000327

AC:

AN:

30592

South Asian (SAS)

AF:

0.0250

AC:

1544

AN:

61726

European-Finnish (FIN)

AF:

0.0127

AC:

405

AN:

31930

Middle Eastern (MID)

AF:

0.0302

AC:

120

AN:

3974

European-Non Finnish (NFE)

AF:

0.0116

AC:

3521

AN:

303184

Other (OTH)

AF:

0.0121

AC:

354

AN:

29348

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.503

Heterozygous variant carriers

361

722

1084

1445

1806

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Exome Het

Exome Hom

Variant carriers

110

<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:

0.00873

AC:

1330

AN:

152346

Hom.:

Cov.:

AF XY:

0.00916

AC XY:

682

AN XY:

74492

show subpopulations

African (AFR)

AF:

0.00202

AC:

AN:

41584

American (AMR)

AF:

0.00738

AC:

113

AN:

15308

Ashkenazi Jewish (ASJ)

AF:

0.0170

AC:

AN:

3472

East Asian (EAS)

AF:

0.00

AC:

AN:

5178

South Asian (SAS)

AF:

0.0228

AC:

110

AN:

4828

European-Finnish (FIN)

AF:

0.0160

AC:

170

AN:

10620

Middle Eastern (MID)

AF:

0.0272

AC:

AN:

294

European-Non Finnish (NFE)

AF:

0.0108

AC:

737

AN:

68038

Other (OTH)

AF:

0.0137

AC:

AN:

2112

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.498

Heterozygous variant carriers

152

228

304

380

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Genome Het

Genome Hom

Variant carriers

110

<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:

0.00526

Hom.:

Bravo

AF:

0.00783

Asia WGS

AF:

0.00549

AC:

AN:

3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

BayesDel_noAF

Benign

-0.22

CADD

Uncertain

(source)

DANN

Benign

0.83

PhyloP100

6.0

Mutation Taster

=100/0

polymorphism

(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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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