rs117495488

Variant names:

• chr19-10420815-C-A
• rs117495488
• NM_001111307.2:c.51C>A

Your query was ambiguous. Multiple possible variants found:

• chr19-10420815-C-A
• chr19-10420815-C-T

Variant summary

Our verdict is Likely benign. The variant received -1 ACMG points: 2P and 3B. PM2 BP4_Moderate BP7

The NM_001111307.2(PDE4A):​c.51C>A​(p.Pro17Pro) variant causes a synonymous change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.000000697 in 1,435,168 control chromosomes in the GnomAD database, with no homozygous occurrence. 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. P17P) has been classified as Benign.

• Frequency:
  • Genomes: not found (cov: 32)
  • Exomes 𝑓: 7.0e-7 (0 hom.)
• Consequence: PDE4A NM_001111307.2 synonymous
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -1.59

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

Our verdict: Likely_benign. The variant received -1 ACMG points.

• PM2: Very rare variant in population databases, with high coverage
• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.32).
• BP7: Synonymous conserved (PhyloP=-1.59 with no splicing effect.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
PDE4A	NM_001111307.2	c.51C>A	p.Pro17Pro	synonymous_variant	Exon 1 of 15	ENST00000380702.7	NP_001104777.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
PDE4A	ENST00000380702.7	c.51C>A	p.Pro17Pro	synonymous_variant	Exon 1 of 15	1	NM_001111307.2	ENSP00000370078.3
PDE4A	ENST00000592685.5	c.254+2950C>A		intron_variant	Intron 3 of 16	1		ENSP00000468507.1

Frequencies

GnomAD3 genomes Cov.: 32

GnomAD4 exome AF: 6.97e-7 AC: 1 AN: 1435168 Hom.: 0 Cov.: 32 AF XY: 0.00000140 AC XY: 1 AN XY: 714056

⚠️ The allele balance in gnomAD version 4 Exomes is significantly skewed from the expected value of 0.5.

African (AFR) AF: 0.00 AC: 0 AN: 31546

American (AMR) AF: 0.00 AC: 0 AN: 43662

Ashkenazi Jewish (ASJ) AF: 0.00 AC: 0 AN: 25630

East Asian (EAS) AF: 0.0000264 AC: 1 AN: 37816

South Asian (SAS) AF: 0.00 AC: 0 AN: 84382

European-Finnish (FIN) AF: 0.00 AC: 0 AN: 39796

Middle Eastern (MID) AF: 0.00 AC: 0 AN: 5710

European-Non Finnish (NFE) AF: 0.00 AC: 0 AN: 1106996

Other (OTH) AF: 0.00 AC: 0 AN: 59630

⚠️ The allele balance in gnomAD4 Exomes is highly skewed from 0.5 (p-value = 0.000000), which strongly suggests a high chance of mosaicism in these individuals.

GnomAD4 genome Cov.: 32

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.32
CADD	Benign	5.3
DANN	Benign	0.90
PhyloP100		-1.6
PromoterAI		-0.017	Neutral

Splicing

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

Publications

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Other links and lift over

dbSNP: rs117495488; hg19: chr19-10531491;