dbSNP rs72624912: IMPDH2:c.910+26A>G (chr3-49026493-T-C) – ACMG Classification: Benign (-8 pts)

Variant summary

Our verdict is Benign. The variant received -8 ACMG points: 0P and 8B. BP4_StrongBS2

The NM_000884.3(IMPDH2):c.910+26A>G variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00743 in 1,604,814 control chromosomes in the GnomAD database, including 139 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 0.0079 ( 20 hom., cov: 32)

Exomes 𝑓: 0.0074 ( 119 hom. )

Consequence

IMPDH2
NM_000884.3 intron

Scores

Clinical Significance

Not reported in ClinVar

Conservation

PhyloP100: 0.237

Publications

3 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 -8 ACMG points.

BP4

Computational evidence support a benign effect (BayesDel_noAF=-0.84).

BS2

High AC in GnomAd4 at 1208 AD gene.

Transcripts

RefSeq

Gene	Transcript	HGVSc	Effect	Exon rank	MANE	Protein	UniProt
IMPDH2	NM_000884.3 link	c.910+26A>G	intron_variant	Intron 8 of 13	ENST00000326739.9	NP_000875.2	P12268A0A384N6C2
IMPDH2	NM_001410759.1 link	c.910+26A>G	intron_variant	Intron 8 of 14		NP_001397688.1
IMPDH2	NM_001410760.1 link	c.835+26A>G	intron_variant	Intron 7 of 13		NP_001397689.1
IMPDH2	NM_001410761.1 link	c.835+26A>G	intron_variant	Intron 7 of 12		NP_001397690.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
IMPDH2	ENST00000326739.9 link	c.910+26A>G		intron_variant	Intron 8 of 13	1	NM_000884.3	ENSP00000321584.4		P12268
ENSG00000290315	ENST00000703936.1 link	c.2950+26A>G		intron_variant	Intron 16 of 21			ENSP00000515567.1		A0A994J749

Frequencies

GnomAD3 genomes

AF:

0.00795

AC:

1209

AN:

152146

Hom.:

Cov.:

show subpopulations

Gnomad AFR

AF:

0.00109

Gnomad AMI

AF:

0.00110

Gnomad AMR

AF:

0.00275

Gnomad ASJ

AF:

0.000865

Gnomad EAS

AF:

0.00

Gnomad SAS

AF:

0.00663

Gnomad FIN

AF:

0.0598

Gnomad MID

AF:

0.00633

Gnomad NFE

AF:

0.00642

Gnomad OTH

AF:

0.00573

GnomAD2 exomes

AF:

0.0104

AC:

2611

AN:

251284

AF XY:

0.0103

show subpopulations

Gnomad AFR exome

AF:

0.000985

Gnomad AMR exome

AF:

0.00263

Gnomad ASJ exome

AF:

0.00218

Gnomad EAS exome

AF:

0.0000544

Gnomad FIN exome

AF:

0.0596

Gnomad NFE exome

AF:

0.00794

Gnomad OTH exome

AF:

0.00930

GnomAD4 exome

AF:

0.00737

AC:

10712

AN:

1452550

Hom.:

119

Cov.:

AF XY:

0.00723

AC XY:

5227

AN XY:

723290

show subpopulations

African (AFR)

AF:

0.000751

AC:

AN:

33296

American (AMR)

AF:

0.00277

AC:

124

AN:

44706

Ashkenazi Jewish (ASJ)

AF:

0.00222

AC:

AN:

26082

East Asian (EAS)

AF:

0.00

AC:

AN:

39668

South Asian (SAS)

AF:

0.00782

AC:

673

AN:

86056

European-Finnish (FIN)

AF:

0.0524

AC:

2798

AN:

53416

Middle Eastern (MID)

AF:

0.0115

AC:

AN:

5756

European-Non Finnish (NFE)

AF:

0.00597

AC:

6586

AN:

1103484

Other (OTH)

AF:

0.00636

AC:

382

AN:

60086

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.503

Heterozygous variant carriers

624

1249

1873

2498

3122

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Exome Het

Exome Hom

Variant carriers

242

484

726

968

1210

<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:

0.00793

AC:

1208

AN:

152264

Hom.:

Cov.:

AF XY:

0.0104

AC XY:

773

AN XY:

74458

show subpopulations

African (AFR)

AF:

0.00108

AC:

AN:

41542

American (AMR)

AF:

0.00275

AC:

AN:

15300

Ashkenazi Jewish (ASJ)

AF:

0.000865

AC:

AN:

3468

East Asian (EAS)

AF:

0.00

AC:

AN:

5184

South Asian (SAS)

AF:

0.00684

AC:

AN:

4822

European-Finnish (FIN)

AF:

0.0598

AC:

635

AN:

10612

Middle Eastern (MID)

AF:

0.00340

AC:

AN:

294

European-Non Finnish (NFE)

AF:

0.00641

AC:

436

AN:

68014

Other (OTH)

AF:

0.00567

AC:

AN:

2116

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.501

Heterozygous variant carriers

118

176

235

294

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Genome Het

Genome 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

Alfa

AF:

0.00585

Hom.:

Bravo

AF:

0.00365

Asia WGS

AF:

0.00173

AC:

AN:

3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

BayesDel_noAF

Benign

-0.84

CADD

Benign

6.0

(source)

DANN

Benign

0.32

PhyloP100

0.24

Mutation Taster

=100/0

polymorphism (auto)

(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