dbSNP rs487278: PDE7B:c.949-537G>A (chr6-136180690-G-A) – ACMG Classification: Benign (-12 pts)

Variant summary

Our verdict is The variant received -12 classification points (ACMG Germline Pathogenicity v2019). BA1BP4_Strong

The NM_018945.4(PDE7B):c.949-537G>A variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a cumulative frequency of 0.49 (AC=74,560) in the gnomAD database across 152,156 control chromosomes, including 20,970 homozygotes. The grpmax filtering allele frequency (95% CI) is 0.668. In-silico predictor (BayesDel (noAF)) classifies this variant as likely benign. Splicing prediction tools (SpliceAI) predict no significant impact on normal splicing. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar.

Frequency

Genomes: 𝑓 0.49 ( 20970 hom., cov: 33)

Consequence

PDE7B
NM_018945.4 intron

Scores

Clinical Significance

Not reported in ClinVar

Conservation

PhyloP100: -0.345

Publications

5 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

new If you want to explore the variant's impact on the transcript NM_018945.4, check out the Mutation Effect Viewer. This is especially useful for frameshift variants or if you want to visualize the effect of exon loss / intron retention.

Classification according to ACMG Germline Pathogenicity v2019

Classification was made for transcript

Our verdict: Benign. The variant received -12 points.

BP4

Computational evidence supports benign — no pathogenic computational or splicing signal (BP4); Splicing verdict: benign (Strong).; Germline computational verdict: benign (Strong).

BA1

GnomAD effective popmax AF >5% — BA1 stand-alone benign; GnomAD reliable popmax AF = 0.6676 — exceeds 5%% threshold (BA1 applied)

Variant Effect in Transcripts

Automated classification analysis was done for transcript: NM_018945.4. You can select a different transcript below to see updated classification assignments.

RefSeq Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	PDE7B	NM_018945.4	MANE Select	c.949-537G>A		intron	N/A	NP_061818.1	Q9NP56

Ensembl Transcripts

Gene	Transcript	Tags	HGVSc	Effect	Exon Rank	Protein	UniProt
PDE7B	ENST00000308191.11	TSL:1 MANE Select	c.949-537G>A	intron	N/A	ENSP00000310661.6	Q9NP56
PDE7B	ENST00000615259.4	TSL:1	c.1105-537G>A	intron	N/A	ENSP00000482117.1	A0A087WYV0
PDE7B-AS1	ENST00000417643.5	TSL:5	n.59-18342C>T	intron	N/A

Frequencies

GnomAD3 genomes

AF:

0.491

AC:

74575

AN:

152038

Hom.:

20982

Cov.:

show subpopulations

Gnomad AFR

AF:

0.195

Gnomad AMI

AF:

0.543

Gnomad AMR

AF:

0.515

Gnomad ASJ

AF:

0.647

Gnomad EAS

AF:

0.592

Gnomad SAS

AF:

0.688

Gnomad FIN

AF:

0.545

Gnomad MID

AF:

0.639

Gnomad NFE

AF:

0.625

Gnomad OTH

AF:

0.515

We have no GnomAD4 exomes data on this position. Probably position not covered by the project.

GnomAD4 genome

AF:

0.490

AC:

74560

AN:

152156

Hom.:

20970

Cov.:

AF XY:

0.494

AC XY:

36717

AN XY:

74382

show subpopulations

African (AFR)

AF:

0.194

AC:

8062

AN:

41530

American (AMR)

AF:

0.515

AC:

7872

AN:

15284

Ashkenazi Jewish (ASJ)

AF:

0.647

AC:

2245

AN:

3472

East Asian (EAS)

AF:

0.591

AC:

3060

AN:

5178

South Asian (SAS)

AF:

0.687

AC:

3316

AN:

4826

European-Finnish (FIN)

AF:

0.545

AC:

5761

AN:

10568

Middle Eastern (MID)

AF:

0.653

AC:

192

AN:

294

European-Non Finnish (NFE)

AF:

0.625

AC:

42477

AN:

67982

Other (OTH)

AF:

0.512

AC:

1081

AN:

2112

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.504

Heterozygous variant carriers

1721

3442

5162

6883

8604

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Genome Het

Genome Hom

Variant carriers

672

1344

2016

2688

3360

<30

30-35

35-40

40-45

45-50

50-55

55-60

60-65

65-70

70-75

75-80

>80

Age

TOPMed (Bravo)

AF:

0.473

ALFA (dbGaP/dbSNP Allele Frequency Aggregator)

AF:

0.564

AC:

143075

AN:

253682

Hom.:

43036

Local populations

ABraOM SABE-WGS-1171

AF:

0.538

AC:

1260

AN:

2342

Hom.:

363

ChinaMAP Phase 1

AF:

0.650

Denmark Genome

AF:

0.667

AC:

200

AN:

300

GenomeAsia100K

AF:

0.585

AC:

2036

AN:

3478

show subpopulations

Oceania

AF:

0.459

AC:

AN:

148

Hom.:

North-East Asia

AF:

0.603

AC:

423

AN:

702

Hom.:

125

South-East Asia

AF:

0.516

AC:

357

AN:

692

Hom.:

South Asia

AF:

0.675

AC:

978

AN:

1448

Hom.:

341

Africa

AF:

0.154

AC:

AN:

208

Hom.:

America

AF:

0.481

AC:

AN:

Hom.:

West Eurasia

AF:

0.671

AC:

153

AN:

228

Hom.:

Korea4K (4,157 Koreans)

AF:

0.619

AC:

4477

AN:

7234

Qatari Genome

AF:

0.636

AC:

112

AN:

176

ToMMo 61KJPN (+60KJPN MNV)

AF:

0.538

AC:

66016

AN:

122818

Hom.:

17730

Turkish Variome

AF:

0.697

AC:

1077

AN:

1546

Hom.:

382

UK10K

AF:

0.643

AC:

4866

AN:

7562

show subpopulations

TwinsUK

AF:

0.642

AC:

2295

AN:

3574

ALSPAC

AF:

0.643

AC:

2477

AN:

3854

WBBC (Westlake BioBank for Chinese) pilot

AF:

0.623

AC:

5580

AN:

8960

Hom.:

1763

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name

Calibrated prediction

Score

Prediction

BayesDel_noAF

Benign

-0.88

CADD

Benign

0.90

(source)

DANN

Benign

0.33

PhyloP100

-0.34

AlphaGenome AVI

Benign

2.7

(source)

GPN-Star LLR

-0.74

(source)

GPN-Star score

0.74

(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

Pangolin (max)

Benign

0.0

(source)

Find out detailed SpliceAI scores and Pangolin per-transcript scores at spliceailookup.broadinstitute.org

MaxEntScan Visualizer can be used to analyze the impact of this mutation on the neighboring sequence.

Publications

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Variant summary

Frequency

Consequence

Scores

Clinical Significance

Conservation

Publications

Classification according to ACMG Germline Pathogenicity v2019

Variant Effect in Transcripts

RefSeq Transcripts

Ensembl Transcripts

Frequencies

Age Distribution

Local populations

ClinVar

Computational scores

Splicing

Publications

Other links and lift over