rs1051738

Variant names:

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

Your query was ambiguous. Multiple possible variants found:

• chr19-10467167-C-A
• chr19-10467167-C-G
• chr19-10467167-C-T

Variant summary

Our verdict is Benign. The variant received -12 ACMG points: 0P and 12B. BP4_Strong BA1

The NM_001111307.2(PDE4A):​c.2207C>A​(p.Ala736Glu) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.181 in 1,613,952 control chromosomes in the GnomAD database, including 27,859 homozygotes. In-silico tool predicts a benign outcome for this variant. 16/20 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 0.20 (3433 hom., cov: 31)
  • Exomes 𝑓: 0.18 (24426 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 -12 ACMG points.

• BP4: Computational evidence support a benign effect (MetaRNN=0.0049764514).
• BA1: GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.284 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

Selected	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	PDE4A	NM_001111307.2	MANE Select	c.2207C>A	p.Ala736Glu	missense	Exon 15 of 15	NP_001104777.1
	PDE4A	NM_001243121.2		c.2141C>A	p.Ala714Glu	missense	Exon 17 of 17	NP_001230050.1
	PDE4A	NM_001111308.1		c.2129C>A	p.Ala710Glu	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>A	p.Ala736Glu	missense	Exon 15 of 15	ENSP00000370078.3
	PDE4A	ENST00000592685.5	TSL:1	c.2141C>A	p.Ala714Glu	missense	Exon 17 of 17	ENSP00000468507.1
	PDE4A	ENST00000293683.9	TSL:1	c.2129C>A	p.Ala710Glu	missense	Exon 15 of 15	ENSP00000293683.4

Frequencies

GnomAD3 genomes AF: 0.202 AC: 30746 AN: 152026 Hom.: 3426 Cov.: 31

Gnomad AFR AF: 0.288

Gnomad AMI AF: 0.305

Gnomad AMR AF: 0.143

Gnomad ASJ AF: 0.203

Gnomad EAS AF: 0.138

Gnomad SAS AF: 0.154

Gnomad FIN AF: 0.123

Gnomad MID AF: 0.177

Gnomad NFE AF: 0.183

Gnomad OTH AF: 0.202

GnomAD2 exomes AF: 0.169 AC: 42579 AN: 251318 AF XY: 0.168

Gnomad AFR exome AF: 0.294

Gnomad AMR exome AF: 0.113

Gnomad ASJ exome AF: 0.179

Gnomad EAS exome AF: 0.148

Gnomad FIN exome AF: 0.126

Gnomad NFE exome AF: 0.183

Gnomad OTH exome AF: 0.161

GnomAD4 exome AF: 0.179 AC: 261775 AN: 1461808 Hom.: 24426 Cov.: 34 AF XY: 0.178 AC XY: 129351 AN XY: 727208

African (AFR) AF: 0.295 AC: 9870 AN: 33480

American (AMR) AF: 0.115 AC: 5121 AN: 44724

Ashkenazi Jewish (ASJ) AF: 0.182 AC: 4749 AN: 26136

East Asian (EAS) AF: 0.0984 AC: 3906 AN: 39698

South Asian (SAS) AF: 0.156 AC: 13487 AN: 86256

European-Finnish (FIN) AF: 0.130 AC: 6933 AN: 53408

Middle Eastern (MID) AF: 0.204 AC: 1176 AN: 5768

European-Non Finnish (NFE) AF: 0.185 AC: 205550 AN: 1111944

Other (OTH) AF: 0.182 AC: 10983 AN: 60394

GnomAD4 genome AF: 0.202 AC: 30774 AN: 152144 Hom.: 3433 Cov.: 31 AF XY: 0.198 AC XY: 14761 AN XY: 74384

African (AFR) AF: 0.288 AC: 11953 AN: 41500

American (AMR) AF: 0.143 AC: 2186 AN: 15268

Ashkenazi Jewish (ASJ) AF: 0.203 AC: 704 AN: 3470

East Asian (EAS) AF: 0.138 AC: 716 AN: 5180

South Asian (SAS) AF: 0.154 AC: 741 AN: 4820

European-Finnish (FIN) AF: 0.123 AC: 1300 AN: 10594

Middle Eastern (MID) AF: 0.184 AC: 54 AN: 294

European-Non Finnish (NFE) AF: 0.183 AC: 12419 AN: 67990

Other (OTH) AF: 0.200 AC: 423 AN: 2116

Alfa AF: 0.185 Hom.: 9370

Bravo AF: 0.209

TwinsUK AF: 0.183 AC: 678

ALSPAC AF: 0.188 AC: 723

ESP6500AA AF: 0.286 AC: 1259

ESP6500EA AF: 0.179 AC: 1536

ExAC AF: 0.176 AC: 21416

Asia WGS AF: 0.127 AC: 440 AN: 3478

EpiCase AF: 0.188

EpiControl AF: 0.182

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
AlphaMissense	Benign	0.093
BayesDel_addAF	Benign	-0.68	T
BayesDel_noAF	Benign	-0.60
CADD	Benign	1.1
DANN	Benign	0.88
DEOGEN2	Benign	0.027	T
Eigen	Benign	-1.3
Eigen_PC	Benign	-1.4
FATHMM_MKL	Benign	0.056	N
LIST_S2	Benign	0.76	T
MetaRNN	Benign	0.0050	T
MetaSVM	Benign	-1.1	T
MutationAssessor	Benign	0.69	N
PhyloP100		-1.5
PrimateAI	Benign	0.27	T
PROVEAN	Benign	0.070	N
REVEL	Benign	0.043
Sift	Uncertain	0.021	D
Sift4G	Benign	0.27	T
Polyphen		0.22	B
Vest4		0.040
ClinPred		0.0075	T
GERP RS		-4.4
Varity_R		0.073
Mutation Taster		=95/5	polymorphism (auto)

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; COSMIC: COSV53352220;