chr1-66365687-G-A

Variant names:

• chr1-66365687-G-A
• rs783036
• NM_002600.4:c.1305G>A

Variant summary

Our verdict is Benign. The variant received -13 ACMG points: 0P and 13B. BP4_Strong BP7 BA1

The NM_002600.4(PDE4B):​c.1305G>A​(p.Glu435Glu) variant causes a synonymous change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.489 in 1,603,504 control chromosomes in the GnomAD database, including 198,180 homozygotes. In-silico tool predicts a benign outcome for this variant. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar.

• Frequency:
  • Genomes: 𝑓 0.55 (24695 hom., cov: 32)
  • Exomes 𝑓: 0.48 (173485 hom.)
• Consequence: PDE4B NM_002600.4 synonymous
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 0.313
• Publications: 21 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: Benign. The variant received -13 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.5).
• BP7: Synonymous conserved (PhyloP=0.313 with no splicing effect.
• BA1: GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.747 is higher than 0.05.

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

Selected	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	PDE4B	NM_002600.4	MANE Select	c.1305G>A	p.Glu435Glu	synonymous	Exon 13 of 17	NP_002591.2
	PDE4B	NM_001037341.2		c.1305G>A	p.Glu435Glu	synonymous	Exon 13 of 17	NP_001032418.1
	PDE4B	NM_001037340.3		c.1260G>A	p.Glu420Glu	synonymous	Exon 11 of 15	NP_001032417.1

Ensembl Transcripts

Selected	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	PDE4B	ENST00000341517.9	TSL:1 MANE Select	c.1305G>A	p.Glu435Glu	synonymous	Exon 13 of 17	ENSP00000342637.4
	PDE4B	ENST00000329654.8	TSL:1	c.1305G>A	p.Glu435Glu	synonymous	Exon 13 of 17	ENSP00000332116.4
	PDE4B	ENST00000423207.6	TSL:1	c.1260G>A	p.Glu420Glu	synonymous	Exon 11 of 15	ENSP00000392947.2

Frequencies

GnomAD3 genomes AF: 0.551 AC: 83731 AN: 151930 Hom.: 24653 Cov.: 32

Gnomad AFR AF: 0.754

Gnomad AMI AF: 0.419

Gnomad AMR AF: 0.508

Gnomad ASJ AF: 0.486

Gnomad EAS AF: 0.142

Gnomad SAS AF: 0.550

Gnomad FIN AF: 0.485

Gnomad MID AF: 0.528

Gnomad NFE AF: 0.485

Gnomad OTH AF: 0.529

GnomAD2 exomes AF: 0.481 AC: 120240 AN: 249924 AF XY: 0.480

Gnomad AFR exome AF: 0.761

Gnomad AMR exome AF: 0.486

Gnomad ASJ exome AF: 0.501

Gnomad EAS exome AF: 0.132

Gnomad FIN exome AF: 0.478

Gnomad NFE exome AF: 0.479

Gnomad OTH exome AF: 0.468

GnomAD4 exome AF: 0.482 AC: 700211 AN: 1451456 Hom.: 173485 Cov.: 31 AF XY: 0.483 AC XY: 348169 AN XY: 721184

African (AFR) AF: 0.777 AC: 25881 AN: 33324

American (AMR) AF: 0.484 AC: 21549 AN: 44534

Ashkenazi Jewish (ASJ) AF: 0.492 AC: 12808 AN: 26034

East Asian (EAS) AF: 0.148 AC: 5871 AN: 39576

South Asian (SAS) AF: 0.539 AC: 46064 AN: 85448

European-Finnish (FIN) AF: 0.482 AC: 25657 AN: 53198

Middle Eastern (MID) AF: 0.482 AC: 2764 AN: 5736

European-Non Finnish (NFE) AF: 0.481 AC: 530775 AN: 1103640

Other (OTH) AF: 0.481 AC: 28842 AN: 59966

GnomAD4 genome AF: 0.551 AC: 83828 AN: 152048 Hom.: 24695 Cov.: 32 AF XY: 0.548 AC XY: 40687 AN XY: 74292

African (AFR) AF: 0.754 AC: 31273 AN: 41476

American (AMR) AF: 0.507 AC: 7739 AN: 15258

Ashkenazi Jewish (ASJ) AF: 0.486 AC: 1687 AN: 3472

East Asian (EAS) AF: 0.142 AC: 734 AN: 5170

South Asian (SAS) AF: 0.550 AC: 2654 AN: 4824

European-Finnish (FIN) AF: 0.485 AC: 5122 AN: 10558

Middle Eastern (MID) AF: 0.544 AC: 160 AN: 294

European-Non Finnish (NFE) AF: 0.485 AC: 32953 AN: 67972

Other (OTH) AF: 0.532 AC: 1124 AN: 2112

Alfa AF: 0.501 Hom.: 41892

Bravo AF: 0.556

Asia WGS AF: 0.436 AC: 1517 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.50
CADD	Benign	6.9
DANN	Benign	0.85
PhyloP100		0.31
Mutation Taster		=93/7	polymorphism (auto)

Splicing

Name	Calibrated prediction	Score	Prediction
SpliceAI score (max)		0.020		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: rs783036; hg19: chr1-66831370; COSMIC: COSV58467637; COSMIC: COSV58467637;