Genetic Variant PDE7B:p.His262His (chr6-136173871-T-C) – ACMG Classification: Benign (-14 pts)

Variant summary

Our verdict is Benign. The variant received -14 ACMG points: 0P and 14B. BP4_StrongBP6_ModerateBA1

The NM_018945.4(PDE7B):c.786T>C(p.His262His) variant causes a synonymous change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00571 in 1,611,710 control chromosomes in the GnomAD database, including 365 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★).

Frequency

Genomes: 𝑓 0.028 ( 194 hom., cov: 32)

Exomes 𝑓: 0.0033 ( 171 hom. )

Consequence

PDE7B
NM_018945.4 synonymous

Scores

Clinical Significance

Benign criteria provided, single submitter B:1

Conservation

PhyloP100: 0.507

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 -14 ACMG points.

BP4

Computational evidence support a benign effect (BayesDel_noAF=-0.67).

BP6

Variant 6-136173871-T-C is Benign according to our data. Variant chr6-136173871-T-C is described in ClinVar as [Benign]. Clinvar id is 792055.Status of the report is criteria_provided_single_submitter, 1 stars.

BA1

GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.0955 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
PDE7B	NM_018945.4 link	c.786T>C	p.His262His	synonymous_variant	Exon 9 of 13	ENST00000308191.11	NP_061818.1	Q9NP56

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
PDE7B	ENST00000308191.11 link	c.786T>C	p.His262His	synonymous_variant	Exon 9 of 13	1	NM_018945.4	ENSP00000310661.6		Q9NP56

Frequencies

GnomAD3 genomes

AF:

0.0283

AC:

4299

AN:

152172

Hom.:

190

Cov.:

show subpopulations

Gnomad AFR

AF:

0.0974

Gnomad AMI

AF:

0.00

Gnomad AMR

AF:

0.0108

Gnomad ASJ

AF:

0.000288

Gnomad EAS

AF:

0.00

Gnomad SAS

AF:

0.000207

Gnomad FIN

AF:

0.00

Gnomad MID

AF:

0.00949

Gnomad NFE

AF:

0.000720

Gnomad OTH

AF:

0.0215

GnomAD2 exomes

AF:

0.00755

AC:

1894

AN:

250784

AF XY:

0.00555

show subpopulations

Gnomad AFR exome

AF:

0.0974

Gnomad AMR exome

AF:

0.00598

Gnomad ASJ exome

AF:

0.0000993

Gnomad EAS exome

AF:

0.0000544

Gnomad FIN exome

AF:

0.00

Gnomad NFE exome

AF:

0.000627

Gnomad OTH exome

AF:

0.00392

GnomAD4 exome

AF:

0.00333

AC:

4859

AN:

1459420

Hom.:

171

Cov.:

AF XY:

0.00291

AC XY:

2113

AN XY:

726218

show subpopulations

African (AFR)

AF:

0.0990

AC:

3302

AN:

33362

American (AMR)

AF:

0.00659

AC:

294

AN:

44626

Ashkenazi Jewish (ASJ)

AF:

0.00

AC:

AN:

26102

East Asian (EAS)

AF:

0.0000252

AC:

AN:

39692

South Asian (SAS)

AF:

0.000267

AC:

AN:

86222

European-Finnish (FIN)

AF:

0.00

AC:

AN:

53390

Middle Eastern (MID)

AF:

0.0110

AC:

AN:

5752

European-Non Finnish (NFE)

AF:

0.000647

AC:

718

AN:

1109966

Other (OTH)

AF:

0.00759

AC:

458

AN:

60308

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.474

Heterozygous variant carriers

206

412

617

823

1029

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

GnomAD4 genome

AF:

0.0285

AC:

4336

AN:

152290

Hom.:

194

Cov.:

AF XY:

0.0278

AC XY:

2069

AN XY:

74492

show subpopulations

African (AFR)

AF:

0.0980

AC:

4072

AN:

41542

American (AMR)

AF:

0.0108

AC:

165

AN:

15298

Ashkenazi Jewish (ASJ)

AF:

0.000288

AC:

AN:

3470

East Asian (EAS)

AF:

0.00

AC:

AN:

5186

South Asian (SAS)

AF:

0.000207

AC:

AN:

4832

European-Finnish (FIN)

AF:

0.00

AC:

AN:

10622

Middle Eastern (MID)

AF:

0.0102

AC:

AN:

294

European-Non Finnish (NFE)

AF:

0.000720

AC:

AN:

68020

Other (OTH)

AF:

0.0213

AC:

AN:

2114

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.501

Heterozygous variant carriers

208

416

623

831

1039

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Alfa

AF:

0.0102

Hom.:

135

Bravo

AF:

0.0320

Asia WGS

AF:

0.0130

AC:

AN:

3478

EpiCase

AF:

0.000928

EpiControl

AF:

0.00101

ClinVar

Significance: Benign

Submissions summary: Benign:1

Revision: criteria provided, single submitter

LINK: link

Submissions by phenotype

not provided

Benign:1

Aug 20, 2018

Labcorp Genetics (formerly Invitae), Labcorp

Significance:Benign

Review Status:criteria provided, single submitter

Collection Method:clinical testing

- -

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

BayesDel_noAF

Benign

-0.67

CADD

Benign

7.6

(source)

DANN

Benign

0.66

PhyloP100

0.51

Mutation Taster

=99/1

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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6-136173871-T-C

Variant summary

Frequency

Consequence

Scores

Clinical Significance

Conservation

ACMG classification

Transcripts

RefSeq

Ensembl

Frequencies

Age Distribution

Age Distribution

ClinVar

Submissions by phenotype

Computational scores

Splicing

Publications

Other links and lift over