chr19-18210463-A-G

Variant names:

• chr19-18210463-A-G
• rs7259012
• NM_001098818.4:c.*466T>C

Variant summary

Our verdict is Benign. Variant got -12 ACMG points: 0P and 12B. BP4_Strong BA1

The NM_001098818.4(PDE4C):​c.*466T>C variant causes a 3 prime UTR change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.654 in 152,724 control chromosomes in the GnomAD database, including 33,225 homozygotes. In-silico tool predicts a benign outcome for this variant. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar.

• Frequency:
  • Genomes: 𝑓 0.65 (33083 hom., cov: 33)
  • Exomes 𝑓: 0.67 (142 hom.)
• Consequence: PDE4C NM_001098818.4 3_prime_UTR
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -1.07

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 -12 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.96).
• BA1: GnomAd4 highest subpopulation (NFE) allele frequency at 95% confidence interval = 0.697 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
PDE4C	NM_001098818.4	c.*466T>C		3_prime_UTR_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	c.*466T>C		3_prime_UTR_variant	Exon 15 of 15	1	NM_001098818.4	ENSP00000262805.10
ENSG00000285188	ENST00000355502	c.*466T>C		3_prime_UTR_variant	Exon 19 of 19	2		ENSP00000347689.2

Frequencies

GnomAD3 genomes AF: 0.654 AC: 99339 AN: 152000 Hom.: 33055 Cov.: 33

Gnomad AFR AF: 0.527

Gnomad AMI AF: 0.739

Gnomad AMR AF: 0.675

Gnomad ASJ AF: 0.665

Gnomad EAS AF: 0.688

Gnomad SAS AF: 0.555

Gnomad FIN AF: 0.817

Gnomad MID AF: 0.627

Gnomad NFE AF: 0.703

Gnomad OTH AF: 0.654

GnomAD4 exome AF: 0.668 AC: 405 AN: 606 Hom.: 142 Cov.: 0 AF XY: 0.690 AC XY: 232 AN XY: 336

Gnomad4 AFR exome AF: 0.357

Gnomad4 AMR exome AF: 0.571

Gnomad4 ASJ exome AF: 0.750

Gnomad4 EAS exome AF: 0.667

Gnomad4 SAS exome AF: 0.750

Gnomad4 FIN exome AF: 0.889

Gnomad4 NFE exome AF: 0.675

Gnomad4 OTH exome AF: 0.571

GnomAD4 genome AF: 0.654 AC: 99420 AN: 152118 Hom.: 33083 Cov.: 33 AF XY: 0.657 AC XY: 48890 AN XY: 74360

Gnomad4 AFR AF: 0.528

Gnomad4 AMR AF: 0.675

Gnomad4 ASJ AF: 0.665

Gnomad4 EAS AF: 0.688

Gnomad4 SAS AF: 0.555

Gnomad4 FIN AF: 0.817

Gnomad4 NFE AF: 0.703

Gnomad4 OTH AF: 0.657

Alfa AF: 0.691 Hom.: 35944

Bravo AF: 0.641

Asia WGS AF: 0.633 AC: 2204 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.96
CADD	Benign	0.79
DANN	Benign	0.34

Splicing

Name	Calibrated prediction	Score	Prediction
SpliceAI score (max)		0.010		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: rs7259012; hg19: chr19-18321273;