rs1484885343

Variant names:

• chr19-10457976-T-A
• rs1484885343
• NM_001111307.2:c.975T>A

Your query was ambiguous. Multiple possible variants found:

• chr19-10457976-T-A
• chr19-10457976-T-C

Variant summary

Our verdict is Likely benign. Variant got -5 ACMG points: 0P and 5B. BP4_Strong BP7

The NM_001111307.2(PDE4A):​c.975T>A​(p.Pro325Pro) variant causes a synonymous change involving the alteration of a non-conserved nucleotide. The variant was absent in control chromosomes in GnomAD project. In-silico tool predicts a benign outcome for this variant. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar. Synonymous variant affecting the same amino acid position (i.e. P325P) has been classified as Likely benign.

• Frequency:
  • Genomes: not found (cov: 32)
  • Exomes 𝑓: 0.00031 (0 hom.)
  • Failed GnomAD Quality Control
• Consequence: PDE4A NM_001111307.2 synonymous
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -2.10

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 Likely_benign. Variant got -5 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.88).
• BP7: Synonymous conserved (PhyloP=-2.1 with no splicing effect.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
PDE4A	NM_001111307.2	c.975T>A	p.Pro325Pro	synonymous_variant	Exon 8 of 15	ENST00000380702.7	NP_001104777.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
PDE4A	ENST00000380702.7	c.975T>A	p.Pro325Pro	synonymous_variant	Exon 8 of 15	1	NM_001111307.2	ENSP00000370078.3

Frequencies

GnomAD3 genomes Cov.: 32

GnomAD4 exome Data not reliable, filtered out with message: AS_VQSR AF: 0.000305 AC: 386 AN: 1265048 Hom.: 0 Cov.: 36 AF XY: 0.000285 AC XY: 181 AN XY: 635860

Gnomad4 AFR exome AF: 0.000236

Gnomad4 AMR exome AF: 0.00

Gnomad4 ASJ exome AF: 0.000242

Gnomad4 EAS exome AF: 0.0000259

Gnomad4 SAS exome AF: 0.0000728

Gnomad4 FIN exome AF: 0.00

Gnomad4 NFE exome AF: 0.000381

Gnomad4 OTH exome AF: 0.000149

GnomAD4 genome Cov.: 32

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.88
CADD	Benign	0.026
DANN	Benign	0.43
RBP_binding_hub_radar		0.0
RBP_regulation_power_radar		1.7

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: rs1484885343; hg19: chr19-10568652;