dbSNP rs9376173: PDE7B:p.Arg6Arg (chr6-136038308-A-C) – ACMG Classification: Benign (-13 pts)

Variant summary

Our verdict is Benign. The variant received -13 ACMG points: 0P and 13B. BP4_StrongBP7BA1

The ENST00000615259.4(PDE7B):c.18A>C(p.Arg6Arg) variant causes a synonymous change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.29 in 1,294,150 control chromosomes in the GnomAD database, including 56,944 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 0.30 ( 7356 hom., cov: 32)

Exomes 𝑓: 0.29 ( 49588 hom. )

Consequence

PDE7B
ENST00000615259.4 synonymous

Scores

Clinical Significance

Not reported in ClinVar

Conservation

PhyloP100: -0.534

Publications

9 publications found

Variant links:

Genes affected

PDE7B (HGNC:8792): (phosphodiesterase 7B) The 3',5'-cyclic nucleotides cAMP and cGMP function as second messengers in a wide variety of signal transduction pathways. 3',5'-cyclic nucleotide phosphodiesterases (PDEs) catalyze the hydrolysis of cAMP and cGMP to the corresponding 5'-monophosphates and provide a mechanism to downregulate cAMP and cGMP signaling. This gene encodes a cAMP-specific phosphodiesterase, a member of the cyclic nucleotide phosphodiesterase family.[provided by RefSeq, Apr 2009]

PDE7B links:

PDE7B-AS1 (HGNC:56334): (PDE7B antisense RNA 1)

PDE7B-AS1 links:

Genome browser will be placed here

ACMG classification

Classification was made for transcript

Our verdict: Benign. The variant received -13 ACMG points.

BP4

Computational evidence support a benign effect (BayesDel_noAF=-0.57).

BP7

Synonymous conserved (PhyloP=-0.534 with no splicing effect.

BA1

GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.518 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
PDE7B	NM_018945.4 link	c.83-70423A>C		intron_variant	Intron 2 of 12	ENST00000308191.11	NP_061818.1	Q9NP56

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	UniProt
PDE7B	ENST00000615259.4 link	c.18A>C	p.Arg6Arg	synonymous_variant	Exon 1 of 12	1		ENSP00000482117.1	A1E5M1
PDE7B	ENST00000308191.11 link	c.83-70423A>C		intron_variant	Intron 2 of 12	1	NM_018945.4	ENSP00000310661.6	Q9NP56
PDE7B-AS1	ENST00000576956.3 link	n.617-3013T>G		intron_variant	Intron 4 of 4	5
PDE7B-AS1	ENST00000626414.1 link	n.74-25595T>G		intron_variant	Intron 1 of 3	5

Frequencies

GnomAD3 genomes

AF:

0.299

AC:

45412

AN:

151876

Hom.:

7351

Cov.:

show subpopulations

Gnomad AFR

AF:

0.227

Gnomad AMI

AF:

0.386

Gnomad AMR

AF:

0.409

Gnomad ASJ

AF:

0.294

Gnomad EAS

AF:

0.534

Gnomad SAS

AF:

0.183

Gnomad FIN

AF:

0.412

Gnomad MID

AF:

0.307

Gnomad NFE

AF:

0.289

Gnomad OTH

AF:

0.320

GnomAD2 exomes

AF:

0.332

AC:

45923

AN:

138286

AF XY:

0.312

show subpopulations

Gnomad AFR exome

AF:

0.219

Gnomad AMR exome

AF:

0.498

Gnomad ASJ exome

AF:

0.280

Gnomad EAS exome

AF:

0.534

Gnomad FIN exome

AF:

0.395

Gnomad NFE exome

AF:

0.294

Gnomad OTH exome

AF:

0.335

GnomAD4 exome

AF:

0.289

AC:

329917

AN:

1142156

Hom.:

49588

Cov.:

AF XY:

0.284

AC XY:

159088

AN XY:

560610

show subpopulations

African (AFR)

AF:

0.222

AC:

5427

AN:

24466

American (AMR)

AF:

0.495

AC:

14072

AN:

28428

Ashkenazi Jewish (ASJ)

AF:

0.284

AC:

4538

AN:

16000

East Asian (EAS)

AF:

0.541

AC:

7154

AN:

13232

South Asian (SAS)

AF:

0.176

AC:

13539

AN:

77086

European-Finnish (FIN)

AF:

0.392

AC:

5521

AN:

14074

Middle Eastern (MID)

AF:

0.297

AC:

1310

AN:

4410

European-Non Finnish (NFE)

AF:

0.288

AC:

266125

AN:

922674

Other (OTH)

AF:

0.293

AC:

12231

AN:

41786

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.487

Heterozygous variant carriers

16417

32834

49252

65669

82086

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Exome Het

Exome Hom

Variant carriers

10258

20516

30774

41032

51290

<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:

0.299

AC:

45443

AN:

151994

Hom.:

7356

Cov.:

AF XY:

0.308

AC XY:

22839

AN XY:

74258

show subpopulations

African (AFR)

AF:

0.227

AC:

9433

AN:

41474

American (AMR)

AF:

0.409

AC:

6252

AN:

15276

Ashkenazi Jewish (ASJ)

AF:

0.294

AC:

1020

AN:

3472

East Asian (EAS)

AF:

0.535

AC:

2741

AN:

5122

South Asian (SAS)

AF:

0.184

AC:

886

AN:

4826

European-Finnish (FIN)

AF:

0.412

AC:

4338

AN:

10532

Middle Eastern (MID)

AF:

0.306

AC:

AN:

294

European-Non Finnish (NFE)

AF:

0.289

AC:

19656

AN:

67972

Other (OTH)

AF:

0.319

AC:

675

AN:

2114

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.504

Heterozygous variant carriers

1602

3204

4807

6409

8011

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Genome Het

Genome Hom

Variant carriers

446

892

1338

1784

2230

<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:

0.296

Hom.:

22491

Bravo

AF:

0.306

Asia WGS

AF:

0.340

AC:

1183

AN:

3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

BayesDel_noAF

Benign

-0.57

CADD

Benign

(source)

DANN

Benign

0.64

PhyloP100

-0.53

PromoterAI

-0.067

Neutral

(source)

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