1-66183851-C-T

Variant names:

• chr1-66183851-C-T
• rs1338719
• NM_002600.4:c.282-63609C>T

Variant summary

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

The NM_002600.4(PDE4B):​c.282-63609C>T variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.497 in 151,980 control chromosomes in the GnomAD database, including 19,495 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 0.50 (19495 hom., cov: 32)
• Consequence: PDE4B NM_002600.4 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 0.505
• Publications: 2 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 -12 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.81).
• BA1: GnomAd4 highest subpopulation (SAS) allele frequency at 95% confidence interval = 0.613 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.282-63609C>T		intron	N/A	NP_002591.2
	PDE4B	NM_001037341.2		c.282-63609C>T		intron	N/A	NP_001032418.1
	PDE4B	NM_001037340.3		c.237-63609C>T		intron	N/A	NP_001032417.1

Ensembl Transcripts

Selected	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	PDE4B	ENST00000341517.9	TSL:1 MANE Select	c.282-63609C>T		intron	N/A	ENSP00000342637.4
	PDE4B	ENST00000329654.8	TSL:1	c.282-63609C>T		intron	N/A	ENSP00000332116.4
	PDE4B	ENST00000423207.6	TSL:1	c.237-63609C>T		intron	N/A	ENSP00000392947.2

Frequencies

GnomAD3 genomes AF: 0.497 AC: 75438 AN: 151862 Hom.: 19481 Cov.: 32

Gnomad AFR AF: 0.342

Gnomad AMI AF: 0.520

Gnomad AMR AF: 0.581

Gnomad ASJ AF: 0.520

Gnomad EAS AF: 0.540

Gnomad SAS AF: 0.631

Gnomad FIN AF: 0.595

Gnomad MID AF: 0.566

Gnomad NFE AF: 0.543

Gnomad OTH AF: 0.486

We have no GnomAD4 exomes data on this position. Probably position not covered by the project.

GnomAD4 genome AF: 0.497 AC: 75487 AN: 151980 Hom.: 19495 Cov.: 32 AF XY: 0.502 AC XY: 37269 AN XY: 74284

African (AFR) AF: 0.341 AC: 14159 AN: 41484

American (AMR) AF: 0.582 AC: 8865 AN: 15238

Ashkenazi Jewish (ASJ) AF: 0.520 AC: 1805 AN: 3470

East Asian (EAS) AF: 0.540 AC: 2797 AN: 5176

South Asian (SAS) AF: 0.632 AC: 3047 AN: 4820

European-Finnish (FIN) AF: 0.595 AC: 6277 AN: 10552

Middle Eastern (MID) AF: 0.582 AC: 171 AN: 294

European-Non Finnish (NFE) AF: 0.543 AC: 36871 AN: 67926

Other (OTH) AF: 0.484 AC: 1021 AN: 2108

Alfa AF: 0.533 Hom.: 11071

Bravo AF: 0.484

Asia WGS AF: 0.586 AC: 2035 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.81
CADD	Benign	8.5
DANN	Benign	0.51
PhyloP100		0.51
Mutation Taster		=100/0	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: rs1338719; hg19: chr1-66649534;