NM_001098818.4:c.*466T>C

Variant names:

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

Variant summary

Our verdict is Benign. The variant received -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
• Publications: 13 publications found

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]

PDE4C (HGNC:):

ACMG classification

Our verdict: Benign. The variant received -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.

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_001098818.4. You can select a different transcript below to see updated ACMG assignments.

RefSeq Transcripts

Selected	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	PDE4C	NM_001098818.4	MANE Select	c.*466T>C		3_prime_UTR	Exon 15 of 15	NP_001092288.1
	PDE4C	NM_000923.6		c.*466T>C		3_prime_UTR	Exon 16 of 16	NP_000914.2
	PDE4C	NM_001330172.2		c.*466T>C		3_prime_UTR	Exon 16 of 16	NP_001317101.1

Ensembl Transcripts

Selected	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	PDE4C	ENST00000262805.17	TSL:1 MANE Select	c.*466T>C		3_prime_UTR	Exon 15 of 15	ENSP00000262805.10
	PDE4C	ENST00000355502.7	TSL:2	c.*466T>C		3_prime_UTR	Exon 19 of 19	ENSP00000347689.2
	PDE4C	ENST00000594617.7	TSL:1	c.*466T>C		3_prime_UTR	Exon 16 of 16	ENSP00000469696.1

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

African (AFR) AF: 0.357 AC: 10 AN: 28

American (AMR) AF: 0.571 AC: 16 AN: 28

Ashkenazi Jewish (ASJ) AF: 0.750 AC: 24 AN: 32

East Asian (EAS) AF: 0.667 AC: 12 AN: 18

South Asian (SAS) AF: 0.750 AC: 6 AN: 8

European-Finnish (FIN) AF: 0.889 AC: 32 AN: 36

Middle Eastern (MID) AC: 0 AN: 0

European-Non Finnish (NFE) AF: 0.675 AC: 289 AN: 428

Other (OTH) AF: 0.571 AC: 16 AN: 28

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

African (AFR) AF: 0.528 AC: 21890 AN: 41474

American (AMR) AF: 0.675 AC: 10312 AN: 15274

Ashkenazi Jewish (ASJ) AF: 0.665 AC: 2308 AN: 3470

East Asian (EAS) AF: 0.688 AC: 3560 AN: 5178

South Asian (SAS) AF: 0.555 AC: 2677 AN: 4822

European-Finnish (FIN) AF: 0.817 AC: 8647 AN: 10588

Middle Eastern (MID) AF: 0.622 AC: 183 AN: 294

European-Non Finnish (NFE) AF: 0.703 AC: 47784 AN: 67998

Other (OTH) AF: 0.657 AC: 1385 AN: 2108

Alfa AF: 0.684 Hom.: 46399

Bravo AF: 0.641

Asia WGS AF: 0.633 AC: 2204 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.96
CADD	Benign	0.79
DANN	Benign	0.34
PhyloP100		-1.1
Mutation Taster		=100/0	polymorphism (auto)

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

Other links and lift over

dbSNP: rs7259012; hg19: chr19-18321273;