Variant 19-10420815-C-T details in Genebe, Genetics Data Aggregator

Variant summary

Our verdict is Benign. Variant got -19 ACMG points: 0P and 19B. BP4_ModerateBP6_Very_StrongBP7BS1BS2

The ENST00000380702.7(PDE4A):c.51C>T(p.Pro17=) variant causes a synonymous change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00337 in 1,587,414 control chromosomes in the GnomAD database, including 89 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★★).

Frequency

Genomes: 𝑓 0.0051 ( 14 hom., cov: 32)

Exomes 𝑓: 0.0032 ( 75 hom. )

Consequence

PDE4A
ENST00000380702.7 synonymous

Scores

Clinical Significance

Benign criteria provided, multiple submitters, no conflicts B:2

Conservation

PhyloP100: -1.59

Variant links:

Genes affected

PDE4A (HGNC:8780): (phosphodiesterase 4A) The protein encoded by this gene belongs to the cyclic nucleotide phosphodiesterase (PDE) family, and PDE4 subfamily. This PDE hydrolyzes the second messenger, cAMP, which is a regulator and mediator of a number of cellular responses to extracellular signals. Thus, by regulating the cellular concentration of cAMP, this protein plays a key role in many important physiological processes. Alternatively spliced transcript variants encoding different isoforms have been described for this gene.[provided by RefSeq, Jul 2011]

PDE4A links:

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ACMG classification

Classification made for transcript

Verdict is Benign. Variant got -19 ACMG points.

BP4

Computational evidence support a benign effect (BayesDel_noAF=-0.37).

BP6

Variant 19-10420815-C-T is Benign according to our data. Variant chr19-10420815-C-T is described in ClinVar as [Benign]. Clinvar id is 710380.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars.

BP7

Synonymous conserved (PhyloP=-1.59 with no splicing effect.

BS1

Variant frequency is greater than expected in population eas. gnomad4 allele frequency = 0.00514 (782/152254) while in subpopulation EAS AF= 0.0307 (158/5146). AF 95% confidence interval is 0.0268. There are 14 homozygotes in gnomad4. There are 537 alleles in male gnomad4 subpopulation. Median coverage is 32. This position pass quality control queck.

BS2

High AC in GnomAd4 at 782 AD gene.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
PDE4A	NM_001111307.2 linkuse as main transcript	c.51C>T	p.Pro17=	synonymous_variant	1/15	ENST00000380702.7	NP_001104777.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
PDE4A	ENST00000380702.7 linkuse as main transcript	c.51C>T	p.Pro17=	synonymous_variant	1/15	1	NM_001111307.2	ENSP00000370078		P27815-1
PDE4A	ENST00000592685.5 linkuse as main transcript	c.254+2950C>T		intron_variant		1		ENSP00000468507		P27815-7

Frequencies

GnomAD3 genomes

AF:

0.00515

AC:

784

AN:

152146

Hom.:

Cov.:

show subpopulations

Gnomad AFR

AF:

0.000314

Gnomad AMI

AF:

0.00

Gnomad AMR

AF:

0.00164

Gnomad ASJ

AF:

0.000288

Gnomad EAS

AF:

0.0310

Gnomad SAS

AF:

0.00414

Gnomad FIN

AF:

0.0443

Gnomad MID

AF:

0.00

Gnomad NFE

AF:

0.00125

Gnomad OTH

AF:

0.00478

GnomAD3 exomes

AF:

0.00634

AC:

1287

AN:

203106

Hom.:

AF XY:

0.00641

AC XY:

732

AN XY:

114230

show subpopulations

Gnomad AFR exome

AF:

0.000306

Gnomad AMR exome

AF:

0.000677

Gnomad ASJ exome

AF:

0.000670

Gnomad EAS exome

AF:

0.0327

Gnomad SAS exome

AF:

0.00396

Gnomad FIN exome

AF:

0.0386

Gnomad NFE exome

AF:

0.00163

Gnomad OTH exome

AF:

0.00661

GnomAD4 exome

AF:

0.00318

AC:

4561

AN:

1435160

Hom.:

Cov.:

AF XY:

0.00323

AC XY:

2309

AN XY:

714050

show subpopulations

Gnomad4 AFR exome

AF:

0.000158

Gnomad4 AMR exome

AF:

0.000687

Gnomad4 ASJ exome

AF:

0.000975

Gnomad4 EAS exome

AF:

0.0433

Gnomad4 SAS exome

AF:

0.00354

Gnomad4 FIN exome

AF:

0.0339

Gnomad4 NFE exome

AF:

0.000878

Gnomad4 OTH exome

AF:

0.00387

GnomAD4 genome

AF:

0.00514

AC:

782

AN:

152254

Hom.:

Cov.:

AF XY:

0.00721

AC XY:

537

AN XY:

74434

show subpopulations

Gnomad4 AFR

AF:

0.000313

Gnomad4 AMR

AF:

0.00163

Gnomad4 ASJ

AF:

0.000288

Gnomad4 EAS

AF:

0.0307

Gnomad4 SAS

AF:

0.00414

Gnomad4 FIN

AF:

0.0443

Gnomad4 NFE

AF:

0.00125

Gnomad4 OTH

AF:

0.00473

Alfa

AF:

0.00189

Hom.:

Bravo

AF:

0.00195

Asia WGS

AF:

0.0290

AC:

101

AN:

3468

ClinVar

Significance: Benign

Submissions summary: Benign:2

Revision: criteria provided, multiple submitters, no conflicts

LINK: link

Submissions by phenotype

not provided

Benign:2

Benign, criteria provided, single submitter	not provided	Breakthrough Genomics, Breakthrough Genomics	-	- -
Benign, criteria provided, single submitter	clinical testing	Labcorp Genetics (formerly Invitae), Labcorp	Aug 22, 2018	- -

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

BayesDel_noAF

Benign

-0.37

CADD

Benign

6.7

DANN

Benign

0.93

Splicing

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

Submissions by phenotype

Computational scores

Splicing

Publications

LitVar

Other links and lift over