19-10467167-C-T

Variant names:

• chr19-10467167-C-T
• rs1051738
• NM_001111307.2:c.2207C>T

Variant summary

Our verdict is Benign. The variant received -8 ACMG points: 0P and 8B. BP4_Strong BS2

The NM_001111307.2(PDE4A):​c.2207C>T​(p.Ala736Val) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0000415 in 1,613,930 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a benign outcome for this variant. 17/21 in silico tools predict a benign outcome for this variant. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar.

• Frequency:
  • Genomes: 𝑓 0.000033 (0 hom., cov: 31)
  • Exomes 𝑓: 0.000042 (0 hom.)
• Consequence: PDE4A NM_001111307.2 missense
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -1.49
• Publications: 61 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 -8 ACMG points.

• BP4: Computational evidence support a benign effect (MetaRNN=0.041576594).
• BS2: High AC in GnomAd4 at 5 AD gene.

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

Selected	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	PDE4A	NM_001111307.2	MANE Select	c.2207C>T	p.Ala736Val	missense	Exon 15 of 15	NP_001104777.1
	PDE4A	NM_001243121.2		c.2141C>T	p.Ala714Val	missense	Exon 17 of 17	NP_001230050.1
	PDE4A	NM_001111308.1		c.2129C>T	p.Ala710Val	missense	Exon 15 of 15	NP_001104778.1

Ensembl Transcripts

Selected	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	PDE4A	ENST00000380702.7	TSL:1 MANE Select	c.2207C>T	p.Ala736Val	missense	Exon 15 of 15	ENSP00000370078.3
	PDE4A	ENST00000592685.5	TSL:1	c.2141C>T	p.Ala714Val	missense	Exon 17 of 17	ENSP00000468507.1
	PDE4A	ENST00000293683.9	TSL:1	c.2129C>T	p.Ala710Val	missense	Exon 15 of 15	ENSP00000293683.4

Frequencies

GnomAD3 genomes AF: 0.0000329 AC: 5 AN: 152060 Hom.: 0 Cov.: 31

Gnomad AFR AF: 0.00

Gnomad AMI AF: 0.00

Gnomad AMR AF: 0.00

Gnomad ASJ AF: 0.000576

Gnomad EAS AF: 0.00

Gnomad SAS AF: 0.00

Gnomad FIN AF: 0.00

Gnomad MID AF: 0.00

Gnomad NFE AF: 0.0000294

Gnomad OTH AF: 0.000478

GnomAD2 exomes AF: 0.0000477 AC: 12 AN: 251318 AF XY: 0.0000515

Gnomad AFR exome AF: 0.00

Gnomad AMR exome AF: 0.0000289

Gnomad ASJ exome AF: 0.000397

Gnomad EAS exome AF: 0.00

Gnomad FIN exome AF: 0.00

Gnomad NFE exome AF: 0.0000352

Gnomad OTH exome AF: 0.000489

GnomAD4 exome AF: 0.0000424 AC: 62 AN: 1461870 Hom.: 0 Cov.: 34 AF XY: 0.0000440 AC XY: 32 AN XY: 727230

African (AFR) AF: 0.00 AC: 0 AN: 33480

American (AMR) AF: 0.0000224 AC: 1 AN: 44724

Ashkenazi Jewish (ASJ) AF: 0.000383 AC: 10 AN: 26136

East Asian (EAS) AF: 0.00 AC: 0 AN: 39698

South Asian (SAS) AF: 0.0000348 AC: 3 AN: 86256

European-Finnish (FIN) AF: 0.00 AC: 0 AN: 53408

Middle Eastern (MID) AF: 0.00121 AC: 7 AN: 5768

European-Non Finnish (NFE) AF: 0.0000315 AC: 35 AN: 1112004

Other (OTH) AF: 0.0000993 AC: 6 AN: 60396

GnomAD4 genome AF: 0.0000329 AC: 5 AN: 152060 Hom.: 0 Cov.: 31 AF XY: 0.0000135 AC XY: 1 AN XY: 74274

African (AFR) AF: 0.00 AC: 0 AN: 41400

American (AMR) AF: 0.00 AC: 0 AN: 15250

Ashkenazi Jewish (ASJ) AF: 0.000576 AC: 2 AN: 3470

East Asian (EAS) AF: 0.00 AC: 0 AN: 5192

South Asian (SAS) AF: 0.00 AC: 0 AN: 4824

European-Finnish (FIN) AF: 0.00 AC: 0 AN: 10596

Middle Eastern (MID) AF: 0.00 AC: 0 AN: 316

European-Non Finnish (NFE) AF: 0.0000294 AC: 2 AN: 68006

Other (OTH) AF: 0.000478 AC: 1 AN: 2094

Alfa AF: 0.00000935 Hom.: 9370

ExAC AF: 0.0000494 AC: 6

EpiCase AF: 0.0000545

EpiControl AF: 0.000178

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
AlphaMissense	Benign	0.073
BayesDel_addAF	Benign	-0.36	T
BayesDel_noAF	Benign	-0.59
CADD	Benign	0.24
DANN	Benign	0.90
DEOGEN2	Benign	0.032	T
Eigen	Benign	-1.6
Eigen_PC	Benign	-1.6
FATHMM_MKL	Benign	0.015	N
LIST_S2	Benign	0.71	T
M_CAP	Benign	0.028	D
MetaRNN	Benign	0.042	T
MetaSVM	Benign	-1.0	T
MutationAssessor	Benign	0.69	N
PhyloP100		-1.5
PrimateAI	Benign	0.26	T
PROVEAN	Benign	-0.47	N
REVEL	Benign	0.036
Sift	Benign	0.48	T
Sift4G	Benign	0.26	T
Polyphen		0.0040	B
Vest4		0.035
MVP		0.43
ClinPred		0.015	T
GERP RS		-4.4
Varity_R		0.012
Mutation Taster		=93/7	polymorphism

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

Other links and lift over

dbSNP: rs1051738; hg19: chr19-10577843;