NM_001111307.2:c.837C>T

Variant names:

• chr19-10454882-C-T
• rs62639961
• NM_001111307.2:c.837C>T

Variant summary

Our verdict is Benign. The variant received -21 ACMG points: 0P and 21B. BP4_Strong BP6_Very_Strong BP7 BA1

The NM_001111307.2(PDE4A):​c.837C>T​(p.Ser279Ser) variant causes a synonymous change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00367 in 1,614,060 control chromosomes in the GnomAD database, including 197 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★★).

• Frequency:
  • Genomes: 𝑓 0.020 (107 hom., cov: 32)
  • Exomes 𝑓: 0.0020 (90 hom.)
• Consequence: PDE4A NM_001111307.2 synonymous
• Clinical Significance: Benign criteria provided, multiple submitters, no conflicts B:2
• Conservation: PhyloP100: -2.56
• Publications: 1 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: Benign. The variant received -21 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.48).
• BP6: Variant 19-10454882-C-T is Benign according to our data. Variant chr19-10454882-C-T is described in ClinVar as Benign. ClinVar VariationId is 769956.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars.
• BP7: Synonymous conserved (PhyloP=-2.56 with no splicing effect.
• BA1: GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.0655 is higher than 0.05.

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.837C>T	p.Ser279Ser	synonymous	Exon 7 of 15	NP_001104777.1	P27815-1
	PDE4A	NM_001243121.2		c.771C>T	p.Ser257Ser	synonymous	Exon 9 of 17	NP_001230050.1	P27815-7
	PDE4A	NM_001111308.1		c.759C>T	p.Ser253Ser	synonymous	Exon 7 of 15	NP_001104778.1	P27815-2

Ensembl Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	PDE4A	ENST00000380702.7	TSL:1 MANE Select	c.837C>T	p.Ser279Ser	synonymous	Exon 7 of 15	ENSP00000370078.3	P27815-1
	PDE4A	ENST00000592685.5	TSL:1	c.771C>T	p.Ser257Ser	synonymous	Exon 9 of 17	ENSP00000468507.1	P27815-7
	PDE4A	ENST00000293683.9	TSL:1	c.759C>T	p.Ser253Ser	synonymous	Exon 7 of 15	ENSP00000293683.4	P27815-2

Frequencies

GnomAD3 genomes AF: 0.0196 AC: 2982 AN: 152104 Hom.: 107 Cov.: 32

Gnomad AFR AF: 0.0679

Gnomad AMI AF: 0.00

Gnomad AMR AF: 0.00858

Gnomad ASJ AF: 0.00

Gnomad EAS AF: 0.00

Gnomad SAS AF: 0.00

Gnomad FIN AF: 0.000377

Gnomad MID AF: 0.00

Gnomad NFE AF: 0.000279

Gnomad OTH AF: 0.00812

GnomAD2 exomes AF: 0.00526 AC: 1322 AN: 251492 AF XY: 0.00382

Gnomad AFR exome AF: 0.0696

Gnomad AMR exome AF: 0.00416

Gnomad ASJ exome AF: 0.00

Gnomad EAS exome AF: 0.00

Gnomad FIN exome AF: 0.000277

Gnomad NFE exome AF: 0.000229

Gnomad OTH exome AF: 0.00179

GnomAD4 exome AF: 0.00202 AC: 2948 AN: 1461838 Hom.: 90 Cov.: 31 AF XY: 0.00175 AC XY: 1273 AN XY: 727222

African (AFR) AF: 0.0700 AC: 2343 AN: 33476

American (AMR) AF: 0.00465 AC: 208 AN: 44722

Ashkenazi Jewish (ASJ) AF: 0.00 AC: 0 AN: 26134

East Asian (EAS) AF: 0.00 AC: 0 AN: 39694

South Asian (SAS) AF: 0.0000812 AC: 7 AN: 86256

European-Finnish (FIN) AF: 0.000393 AC: 21 AN: 53412

Middle Eastern (MID) AF: 0.00173 AC: 10 AN: 5768

European-Non Finnish (NFE) AF: 0.000121 AC: 135 AN: 1111986

Other (OTH) AF: 0.00371 AC: 224 AN: 60390

GnomAD4 genome AF: 0.0196 AC: 2978 AN: 152222 Hom.: 107 Cov.: 32 AF XY: 0.0190 AC XY: 1414 AN XY: 74420

African (AFR) AF: 0.0676 AC: 2807 AN: 41520

American (AMR) AF: 0.00857 AC: 131 AN: 15280

Ashkenazi Jewish (ASJ) AF: 0.00 AC: 0 AN: 3472

East Asian (EAS) AF: 0.00 AC: 0 AN: 5168

South Asian (SAS) AF: 0.00 AC: 0 AN: 4822

European-Finnish (FIN) AF: 0.000377 AC: 4 AN: 10614

Middle Eastern (MID) AF: 0.00 AC: 0 AN: 294

European-Non Finnish (NFE) AF: 0.000279 AC: 19 AN: 68026

Other (OTH) AF: 0.00803 AC: 17 AN: 2116

Alfa AF: 0.0103 Hom.: 12

Bravo AF: 0.0225

Asia WGS AF: 0.00404 AC: 14 AN: 3478

EpiCase AF: 0.000109

EpiControl AF: 0.000356

ClinVar

ClinVar submissions

Significance: Benign

Revision: criteria provided, multiple submitters, no conflicts

Pathogenic	VUS	Benign	Condition
-	-	2	not provided (2)

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.48
CADD	Benign	8.3
DANN	Benign	0.83
PhyloP100		-2.6
Mutation Taster		=98/2	polymorphism (auto)

Splicing

Name	Calibrated prediction	Score	Prediction
SpliceAI score (max)		0.050		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: rs62639961; hg19: chr19-10565558; COSMIC: COSV104540881; COSMIC: COSV104540881;