dbSNP rs72624908: IMPDH2:c.148-77C>T (chr3-49028609-G-A) – 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.148-77C>T variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.000586 in 1,380,238 control chromosomes in the GnomAD database, including 4 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 0.0028 ( 4 hom., cov: 33)

Exomes 𝑓: 0.00031 ( 0 hom. )

Consequence

IMPDH2
NM_000884.3 intron

Scores

Clinical Significance

Not reported in ClinVar

Conservation

PhyloP100: -0.0960

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 -8 ACMG points.

BP4

Computational evidence support a benign effect (BayesDel_noAF=-0.82).

BS2

High AC in GnomAd4 at 424 AD gene.

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_000884.3. You can select a different transcript below to see updated ACMG assignments.

RefSeq Transcripts

Gene	Transcript	Tags	HGVSc	Effect	Exon Rank	Protein	UniProt
IMPDH2	NM_000884.3	MANE Select	c.148-77C>T	intron	N/A	NP_000875.2	P12268
IMPDH2	NM_001410759.1		c.148-77C>T	intron	N/A	NP_001397688.1	H0Y4R1
IMPDH2	NM_001410760.1		c.148-77C>T	intron	N/A	NP_001397689.1	A0A7I2YQK5

Ensembl Transcripts

Gene	Transcript	Tags	HGVSc	Effect	Exon Rank	Protein	UniProt
IMPDH2	ENST00000326739.9	TSL:1 MANE Select	c.148-77C>T	intron	N/A	ENSP00000321584.4	P12268
ENSG00000290315	ENST00000703936.1		c.2188-77C>T	intron	N/A	ENSP00000515567.1	A0A994J749
IMPDH2	ENST00000937815.1		c.316-77C>T	intron	N/A	ENSP00000607874.1

Frequencies

GnomAD3 genomes

AF:

0.00279

AC:

424

AN:

152112

Hom.:

Cov.:

show subpopulations

Gnomad AFR

AF:

0.00973

Gnomad AMI

AF:

0.00

Gnomad AMR

AF:

0.000852

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:

0.000103

Gnomad OTH

AF:

0.000478

GnomAD4 exome

AF:

0.000314

AC:

385

AN:

1228008

Hom.:

Cov.:

AF XY:

0.000277

AC XY:

172

AN XY:

621648

show subpopulations

African (AFR)

AF:

0.0101

AC:

290

AN:

28618

American (AMR)

AF:

0.000665

AC:

AN:

43582

Ashkenazi Jewish (ASJ)

AF:

0.00

AC:

AN:

24510

East Asian (EAS)

AF:

0.0000779

AC:

AN:

38518

South Asian (SAS)

AF:

0.00

AC:

AN:

80938

European-Finnish (FIN)

AF:

0.00

AC:

AN:

53038

Middle Eastern (MID)

AF:

0.000188

AC:

AN:

5314

European-Non Finnish (NFE)

AF:

0.0000322

AC:

AN:

900938

Other (OTH)

AF:

0.000628

AC:

AN:

52552

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.494

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:

0.00279

AC:

424

AN:

152230

Hom.:

Cov.:

AF XY:

0.00283

AC XY:

211

AN XY:

74440

show subpopulations

African (AFR)

AF:

0.00971

AC:

403

AN:

41520

American (AMR)

AF:

0.000850

AC:

AN:

15286

Ashkenazi Jewish (ASJ)

AF:

0.00

AC:

AN:

3472

East Asian (EAS)

AF:

0.00

AC:

AN:

5182

South Asian (SAS)

AF:

0.00

AC:

AN:

4822

European-Finnish (FIN)

AF:

0.00

AC:

AN:

10610

Middle Eastern (MID)

AF:

0.00

AC:

AN:

294

European-Non Finnish (NFE)

AF:

0.000103

AC:

AN:

68016

Other (OTH)

AF:

0.000473

AC:

AN:

2116

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.506

Heterozygous variant carriers

114

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:

0.00222

Hom.:

Bravo

AF:

0.00336

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name

Calibrated prediction

Score

Prediction

BayesDel_noAF

Benign

-0.82

CADD

Benign

5.2

(source)

DANN

Benign

0.33

PhyloP100

-0.096

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

Variant Effect in Transcripts

RefSeq Transcripts

Ensembl Transcripts

Frequencies

Age Distribution

Age Distribution

ClinVar

Computational scores

Splicing

Publications

Other links and lift over