19-18210947-G-A

Variant names:

• chr19-18210947-G-A
• rs150088794
• NM_001098818.4:c.2025C>T

Variant summary

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

The NM_001098818.4(PDE4C):​c.2025C>T​(p.Leu675Leu) variant causes a synonymous change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00409 in 1,610,238 control chromosomes in the GnomAD database, including 22 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Likely benign (★).

• Frequency:
  • Genomes: 𝑓 0.0036 (2 hom., cov: 32)
  • Exomes 𝑓: 0.0041 (20 hom.)
• Consequence: PDE4C NM_001098818.4 synonymous
• Clinical Significance: Likely benign criteria provided, single submitter B:1
• Conservation: PhyloP100: -0.235

Genes affected

PDE4C (HGNC:8782): (phosphodiesterase 4C) 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]

ENSG00000285188 (HGNC:):

ACMG classification

Verdict is Benign. Variant got -11 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.85).
• BP6: Variant 19-18210947-G-A is Benign according to our data. Variant chr19-18210947-G-A is described in ClinVar as [Likely_benign]. Clinvar id is 2649575.Status of the report is criteria_provided_single_submitter, 1 stars.
• BP7: Synonymous conserved (PhyloP=-0.235 with no splicing effect.
• BS2: High Homozygotes in GnomAd4 at 2 AR gene

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
PDE4C	NM_001098818.4	c.2025C>T	p.Leu675Leu	synonymous_variant	Exon 15 of 15	ENST00000262805.17	NP_001092288.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
PDE4C	ENST00000262805.17	c.2025C>T	p.Leu675Leu	synonymous_variant	Exon 15 of 15	1	NM_001098818.4	ENSP00000262805.10
ENSG00000285188	ENST00000355502.7	c.2121C>T	p.Leu707Leu	synonymous_variant	Exon 19 of 19	2		ENSP00000347689.2

Frequencies

GnomAD3 genomes AF: 0.00365 AC: 555 AN: 152212 Hom.: 2 Cov.: 32

Gnomad AFR AF: 0.000531

Gnomad AMI AF: 0.00

Gnomad AMR AF: 0.00216

Gnomad ASJ AF: 0.00259

Gnomad EAS AF: 0.00

Gnomad SAS AF: 0.000207

Gnomad FIN AF: 0.00593

Gnomad MID AF: 0.00316

Gnomad NFE AF: 0.00613

Gnomad OTH AF: 0.00430

GnomAD3 exomes AF: 0.00350 AC: 869 AN: 248188 Hom.: 4 AF XY: 0.00330 AC XY: 442 AN XY: 134070

Gnomad AFR exome AF: 0.000739

Gnomad AMR exome AF: 0.00111

Gnomad ASJ exome AF: 0.00329

Gnomad EAS exome AF: 0.0000544

Gnomad SAS exome AF: 0.000764

Gnomad FIN exome AF: 0.00607

Gnomad NFE exome AF: 0.00548

Gnomad OTH exome AF: 0.00331

GnomAD4 exome AF: 0.00414 AC: 6037 AN: 1457908 Hom.: 20 Cov.: 30 AF XY: 0.00408 AC XY: 2954 AN XY: 724866

Gnomad4 AFR exome AF: 0.000718

Gnomad4 AMR exome AF: 0.00124

Gnomad4 ASJ exome AF: 0.00217

Gnomad4 EAS exome AF: 0.0000504

Gnomad4 SAS exome AF: 0.000793

Gnomad4 FIN exome AF: 0.00610

Gnomad4 NFE exome AF: 0.00479

Gnomad4 OTH exome AF: 0.00326

GnomAD4 genome AF: 0.00364 AC: 555 AN: 152330 Hom.: 2 Cov.: 32 AF XY: 0.00332 AC XY: 247 AN XY: 74488

Gnomad4 AFR AF: 0.000529

Gnomad4 AMR AF: 0.00216

Gnomad4 ASJ AF: 0.00259

Gnomad4 EAS AF: 0.00

Gnomad4 SAS AF: 0.000207

Gnomad4 FIN AF: 0.00593

Gnomad4 NFE AF: 0.00613

Gnomad4 OTH AF: 0.00425

Alfa AF: 0.00470 Hom.: 1

Bravo AF: 0.00300

Asia WGS AF: 0.000577 AC: 2 AN: 3478

ClinVar

Significance: Likely benign

Submissions summary: Benign:1

Revision: criteria provided, single submitter

Submissions by phenotype

not provided Benign:1

Aug 01, 2022

CeGaT Center for Human Genetics Tuebingen

Significance: Likely benign

Review Status: criteria provided, single submitter

Collection Method: clinical testing

PDE4C: BP4, BP7 -

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.85
CADD	Benign	0.76
DANN	Benign	0.42

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

LitVar

Other links and lift over

dbSNP: rs150088794; hg19: chr19-18321757;