19-10450899-C-T

Variant summary

Our verdict is Benign. Variant got -11 ACMG points: 0P and 11B. BP4_Strong BP6_Moderate BP7 BS2

The NM_001111307.2(PDE4A):c.741C>T(p.Thr247=) variant causes a synonymous change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00186 in 1,610,780 control chromosomes in the GnomAD database, including 3 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Likely benign (★).

• Frequency:
  • Genomes: 𝑓 0.0015 (1 hom., cov: 32)
  • Exomes 𝑓: 0.0019 (2 hom.)
• Consequence: PDE4A NM_001111307.2 synonymous
• Clinical Significance: Likely benign criteria provided, single submitter B:1
• Conservation: PhyloP100: 0.183

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 -11 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.58).
• BP6: Variant 19-10450899-C-T is Benign according to our data. Variant chr19-10450899-C-T is described in ClinVar as [Likely_benign]. Clinvar id is 2649292.Status of the report is criteria_provided_single_submitter, 1 stars.
• BP7: Synonymous conserved (PhyloP=0.183 with no splicing effect.
• BS2: High AC in GnomAd at 233 AD gene.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
PDE4A	NM_001111307.2	c.741C>T	p.Thr247=	synonymous_variant	6/15	ENST00000380702.7

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
PDE4A	ENST00000380702.7	c.741C>T	p.Thr247=	synonymous_variant	6/15	1	NM_001111307.2

Frequencies

GnomAD3 genomes AF: 0.00153 AC: 233 AN: 152222 Hom.: 1 Cov.: 32

Gnomad AFR AF: 0.000555

Gnomad AMI AF: 0.00

Gnomad AMR AF: 0.000982

Gnomad ASJ AF: 0.00

Gnomad EAS AF: 0.00

Gnomad SAS AF: 0.000207

Gnomad FIN AF: 0.00113

Gnomad MID AF: 0.00

Gnomad NFE AF: 0.00262

Gnomad OTH AF: 0.00191

GnomAD3 exomes AF: 0.00110 AC: 266 AN: 241532 Hom.: 0 AF XY: 0.00113 AC XY: 148 AN XY: 131270

Gnomad AFR exome AF: 0.000338

Gnomad AMR exome AF: 0.000178

Gnomad ASJ exome AF: 0.000102

Gnomad EAS exome AF: 0.00

Gnomad SAS exome AF: 0.000102

Gnomad FIN exome AF: 0.00143

Gnomad NFE exome AF: 0.00197

Gnomad OTH exome AF: 0.00101

GnomAD4 exome AF: 0.00189 AC: 2763 AN: 1458440 Hom.: 2 Cov.: 38 AF XY: 0.00189 AC XY: 1368 AN XY: 725098

Gnomad4 AFR exome AF: 0.000299

Gnomad4 AMR exome AF: 0.000226

Gnomad4 ASJ exome AF: 0.000154

Gnomad4 EAS exome AF: 0.00

Gnomad4 SAS exome AF: 0.0000703

Gnomad4 FIN exome AF: 0.00182

Gnomad4 NFE exome AF: 0.00228

Gnomad4 OTH exome AF: 0.00178

GnomAD4 genome AF: 0.00153 AC: 233 AN: 152340 Hom.: 1 Cov.: 32 AF XY: 0.00152 AC XY: 113 AN XY: 74496

Gnomad4 AFR AF: 0.000553

Gnomad4 AMR AF: 0.000981

Gnomad4 ASJ AF: 0.00

Gnomad4 EAS AF: 0.00

Gnomad4 SAS AF: 0.000207

Gnomad4 FIN AF: 0.00113

Gnomad4 NFE AF: 0.00262

Gnomad4 OTH AF: 0.00189

Alfa AF: 0.00227 Hom.: 1

Bravo AF: 0.00141

ClinVar

Significance: Likely benign

Submissions summary: Benign:1

Revision: criteria provided, single submitter

Submissions by phenotype

not provided Benign:1

Likely benign, criteria provided, single submitter

clinical testing

CeGaT Center for Human Genetics Tuebingen

Mar 01, 2022

PDE4A: BP4, BP7 -

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.58
Cadd	Benign	11
Dann	Benign	0.71
RBP_binding_hub_radar		0.0
RBP_regulation_power_radar		1.7

Splicing

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

Publications

LitVar

Other links and lift over

dbSNP: rs202117812; hg19: chr19-10561575;