NM_001111307.2:c.60G>A

Variant names:

• chr19-10420824-G-A
• rs78392044
• NM_001111307.2:c.60G>A

Variant summary

Our verdict is Likely benign. The variant received -3 ACMG points: 2P and 5B. PM2 BP4_Strong BP7

The NM_001111307.2(PDE4A):​c.60G>A​(p.Arg20Arg) variant causes a synonymous change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00000279 in 1,435,466 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. R20R) has been classified as Benign.

• Frequency:
  • Genomes: not found (cov: 32)
  • Exomes 𝑓: 0.0000028 (0 hom.)
• Consequence: PDE4A NM_001111307.2 synonymous
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 2.48
• Publications: 2 publications found

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 -3 ACMG points.

• PM2: Very rare variant in population databases, with high coverage
• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.48).
• BP7: Synonymous conserved (PhyloP=2.48 with no splicing effect.

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_001111307.2. You can select a different transcript below to see updated ACMG assignments.

RefSeq Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	PDE4A	NM_001111307.2	MANE Select	c.60G>A	p.Arg20Arg	synonymous	Exon 1 of 15	NP_001104777.1	P27815-1
	PDE4A	NM_001243121.2		c.254+2959G>A		intron	N/A	NP_001230050.1	P27815-7

Ensembl Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	PDE4A	ENST00000380702.7	TSL:1 MANE Select	c.60G>A	p.Arg20Arg	synonymous	Exon 1 of 15	ENSP00000370078.3	P27815-1
	PDE4A	ENST00000592685.5	TSL:1	c.254+2959G>A		intron	N/A	ENSP00000468507.1	P27815-7
	PDE4A	ENST00000937031.1		c.60G>A	p.Arg20Arg	synonymous	Exon 1 of 15	ENSP00000607090.1

Frequencies

GnomAD3 genomes Cov.: 32

GnomAD2 exomes AF: 0.00000492 AC: 1 AN: 203312 AF XY: 0.00000874

Gnomad AFR exome AF: 0.00

Gnomad AMR exome AF: 0.00

Gnomad ASJ exome AF: 0.00

Gnomad EAS exome AF: 0.00

Gnomad FIN exome AF: 0.00

Gnomad NFE exome AF: 0.00

Gnomad OTH exome AF: 0.000193

GnomAD4 exome AF: 0.00000279 AC: 4 AN: 1435466 Hom.: 0 Cov.: 32 AF XY: 0.00000420 AC XY: 3 AN XY: 714236

African (AFR) AF: 0.00 AC: 0 AN: 31566

American (AMR) AF: 0.00 AC: 0 AN: 43756

Ashkenazi Jewish (ASJ) AF: 0.00 AC: 0 AN: 25636

East Asian (EAS) AF: 0.00 AC: 0 AN: 37878

South Asian (SAS) AF: 0.00 AC: 0 AN: 84408

European-Finnish (FIN) AF: 0.00 AC: 0 AN: 39772

Middle Eastern (MID) AF: 0.00 AC: 0 AN: 5716

European-Non Finnish (NFE) AF: 0.00000361 AC: 4 AN: 1107096

Other (OTH) AF: 0.00 AC: 0 AN: 59638

GnomAD4 genome Cov.: 32

Alfa AF: 0.0000257 Hom.: 0

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.48
CADD	Benign	8.9
DANN	Benign	0.92
PhyloP100		2.5
PromoterAI		0.011	Neutral

Splicing

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

Other links and lift over

dbSNP: rs78392044; hg19: chr19-10531500;