19-10420815-C-T

Variant summary

Our verdict is Benign. Variant got -13 ACMG points: 0P and 13B. BP4_Moderate BP6_Moderate BP7 BS1 BS2

The NM_001111307.2(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 NM_001111307.2 synonymous
• Clinical Significance: Benign criteria provided, single submitter B:1
• Conservation: PhyloP100: -1.59

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]

ACMG classification

Verdict is Benign. Variant got -13 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_single_submitter, 1 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 GnomAd at 784 AD gene.

Transcripts

RefSeq

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

Ensembl

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

Frequencies

GnomAD3 genomes AF: 0.00515 AC: 784 AN: 152146 Hom.: 14 Cov.: 32

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.: 29 AF XY: 0.00641 AC XY: 732 AN XY: 114230

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.: 75 Cov.: 32 AF XY: 0.00323 AC XY: 2309 AN XY: 714050

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.: 14 Cov.: 32 AF XY: 0.00721 AC XY: 537 AN XY: 74434

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.: 0

Bravo AF: 0.00195

Asia WGS AF: 0.0290 AC: 101 AN: 3468

ClinVar

Significance: Benign

Submissions summary: Benign:1

Revision: criteria provided, single submitter

Submissions by phenotype

not provided Benign:1

Benign, criteria provided, single submitter

clinical testing

Invitae

Aug 22, 2018

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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

Other links and lift over

dbSNP: rs117495488; hg19: chr19-10531491;