NM_002600.4:c.638A>G

Variant names:

• chr1-66332511-A-G
• rs1453424766
• NM_002600.4:c.638A>G

Variant summary

Our verdict is Likely benign. The variant received -3 ACMG points: 1P and 4B. PP3 BS2

The NM_002600.4(PDE4B):​c.638A>G​(p.Glu213Gly) variant causes a missense change involving the alteration of a conserved nucleotide. The variant allele was found at a frequency of 0.00000682 in 1,614,034 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a pathogenic outcome for this variant. Variant has been reported in ClinVar as Uncertain significance (★).

• Frequency:
  • Genomes: 𝑓 0.0000066 (0 hom., cov: 32)
  • Exomes 𝑓: 0.0000068 (0 hom.)
• Consequence: PDE4B NM_002600.4 missense
• Clinical Significance: Uncertain significance criteria provided, single submitter U:1
• Conservation: PhyloP100: 9.21
• Publications: 0 publications found

Genes affected

PDE4B (HGNC:8781): (phosphodiesterase 4B) This gene is a member of the type IV, cyclic AMP (cAMP)-specific, cyclic nucleotide phosphodiesterase (PDE) family. The encoded protein regulates the cellular concentrations of cyclic nucleotides and thereby play a role in signal transduction. Altered activity of this protein has been associated with schizophrenia and bipolar affective disorder. Alternative splicing and the use of alternative promoters results in multiple transcript variants encoding different isoforms. [provided by RefSeq, Jul 2014]

ACMG classification

Our verdict: Likely_benign. The variant received -3 ACMG points.

• PP3: MetaRNN computational evidence supports a deleterious effect, 0.772
• BS2: High AC in GnomAdExome4 at 10 AD gene.

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_002600.4. 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
	PDE4B	NM_002600.4	MANE Select	c.638A>G	p.Glu213Gly	missense	Exon 8 of 17	NP_002591.2
	PDE4B	NM_001037341.2		c.638A>G	p.Glu213Gly	missense	Exon 8 of 17	NP_001032418.1	X5DNX5
	PDE4B	NM_001037340.3		c.593A>G	p.Glu198Gly	missense	Exon 6 of 15	NP_001032417.1	Q07343-3

Ensembl Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	PDE4B	ENST00000341517.9	TSL:1 MANE Select	c.638A>G	p.Glu213Gly	missense	Exon 8 of 17	ENSP00000342637.4	Q07343-1
	PDE4B	ENST00000329654.8	TSL:1	c.638A>G	p.Glu213Gly	missense	Exon 8 of 17	ENSP00000332116.4	Q07343-1
	PDE4B	ENST00000423207.6	TSL:1	c.593A>G	p.Glu198Gly	missense	Exon 6 of 15	ENSP00000392947.2	Q07343-3

Frequencies

GnomAD3 genomes AF: 0.00000657 AC: 1 AN: 152202 Hom.: 0 Cov.: 32

Gnomad AFR AF: 0.00

Gnomad AMI AF: 0.00

Gnomad AMR AF: 0.00

Gnomad ASJ AF: 0.00

Gnomad EAS AF: 0.00

Gnomad SAS AF: 0.00

Gnomad FIN AF: 0.00

Gnomad MID AF: 0.00

Gnomad NFE AF: 0.0000147

Gnomad OTH AF: 0.00

GnomAD4 exome AF: 0.00000684 AC: 10 AN: 1461832 Hom.: 0 Cov.: 32 AF XY: 0.00000413 AC XY: 3 AN XY: 727212

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

American (AMR) AF: 0.00 AC: 0 AN: 44724

Ashkenazi Jewish (ASJ) AF: 0.00 AC: 0 AN: 26136

East Asian (EAS) AF: 0.00 AC: 0 AN: 39700

South Asian (SAS) AF: 0.00 AC: 0 AN: 86258

European-Finnish (FIN) AF: 0.00 AC: 0 AN: 53368

Middle Eastern (MID) AF: 0.00 AC: 0 AN: 5768

European-Non Finnish (NFE) AF: 0.00000899 AC: 10 AN: 1112004

Other (OTH) AF: 0.00 AC: 0 AN: 60394

GnomAD4 genome AF: 0.00000657 AC: 1 AN: 152202 Hom.: 0 Cov.: 32 AF XY: 0.0000134 AC XY: 1 AN XY: 74356

African (AFR) AF: 0.00 AC: 0 AN: 41438

American (AMR) AF: 0.00 AC: 0 AN: 15280

Ashkenazi Jewish (ASJ) AF: 0.00 AC: 0 AN: 3470

East Asian (EAS) AF: 0.00 AC: 0 AN: 5200

South Asian (SAS) AF: 0.00 AC: 0 AN: 4830

European-Finnish (FIN) AF: 0.00 AC: 0 AN: 10622

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

European-Non Finnish (NFE) AF: 0.0000147 AC: 1 AN: 68040

Other (OTH) AF: 0.00 AC: 0 AN: 2094

Alfa AF: 0.0000329 Hom.: 0

Bravo AF: 0.00000756

ClinVar

ClinVar submissions

Significance: Uncertain significance

Revision: criteria provided, single submitter

Pathogenic	VUS	Benign	Condition
-	1	-	not specified (1)

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
AlphaMissense	Benign	0.19
BayesDel_addAF	Pathogenic	0.26	D
BayesDel_noAF	Pathogenic	0.14
CADD	Pathogenic	26
DANN	Uncertain	1.0
DEOGEN2	Uncertain	0.78	D
Eigen	Uncertain	0.44
Eigen_PC	Uncertain	0.52
FATHMM_MKL	Uncertain	0.90	D
LIST_S2	Uncertain	0.95	D
M_CAP	Uncertain	0.13	D
MetaRNN	Pathogenic	0.76	D
MetaSVM	Uncertain	0.089	D
MutationAssessor	Uncertain	2.1	M
PhyloP100		9.2
PrimateAI	Uncertain	0.53	T
PROVEAN	Pathogenic	-4.6	D
REVEL	Uncertain	0.60
Sift	Uncertain	0.0010	D
Sift4G	Uncertain	0.0030	D
Polyphen		0.60	P
Vest4		0.33
MVP		0.67
MPC		0.58
ClinPred		1.0	D
GERP RS		5.2
PromoterAI		0.023	Neutral
Varity_R		0.62
Mutation Taster		=22/78	disease causing

Splicing

Name	Calibrated prediction	Score	Prediction
SpliceAI score (max)		0.010		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: rs1453424766; hg19: chr1-66798194;