Genetic Variant ENST00000615259.4:c.18A>C (chr6-136038308-A-C) – ACMG Classification: Benign (-13 pts)

Variant summary

Our verdict is Benign. Variant got -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

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:

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ACMG classification

Classification made for transcript

Verdict is Benign. Variant got -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

GnomAD3 exomes

AF:

0.332

AC:

45923

AN:

138286

Hom.:

8687

AF XY:

0.312

AC XY:

23412

AN XY:

74940

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 SAS exome

AF:

0.180

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

Gnomad4 AFR exome

AF:

0.222

Gnomad4 AMR exome

AF:

0.495

Gnomad4 ASJ exome

AF:

0.284

Gnomad4 EAS exome

AF:

0.541

Gnomad4 SAS exome

AF:

0.176

Gnomad4 FIN exome

AF:

0.392

Gnomad4 NFE exome

AF:

0.288

Gnomad4 OTH exome

AF:

0.293

GnomAD4 genome

AF:

0.299

AC:

45443

AN:

151994

Hom.:

7356

Cov.:

AF XY:

0.308

AC XY:

22839

AN XY:

74258

show subpopulations

Gnomad4 AFR

AF:

0.227

Gnomad4 AMR

AF:

0.409

Gnomad4 ASJ

AF:

0.294

Gnomad4 EAS

AF:

0.535

Gnomad4 SAS

AF:

0.184

Gnomad4 FIN

AF:

0.412

Gnomad4 NFE

AF:

0.289

Gnomad4 OTH

AF:

0.319

Alfa

AF:

0.292

Hom.:

9504

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

DANN

Benign

0.64

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

LitVar

Below is the list of publications found by LitVar. It may be empty.

Variant summary

Frequency

Consequence

Scores

Clinical Significance

Conservation

ACMG classification

Transcripts

RefSeq

Ensembl

Frequencies

ClinVar

Computational scores

Splicing

Publications

LitVar

Other links and lift over