chr1-66206849-C-A

Position:

• chr1-66206849-C-A

Variant summary

Our verdict is Benign. Variant got -12 ACMG points: 0P and 12B. BP4_Strong BA1

The NM_002600.4(PDE4B):​c.282-40611C>A variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.487 in 151,962 control chromosomes in the GnomAD database, including 19,150 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 0.49 (19150 hom., cov: 31)
• Consequence: PDE4B NM_002600.4 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -1.40

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

Verdict is Benign. Variant got -12 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.85).
• BA1: GnomAd4 highest subpopulation (SAS) allele frequency at 95% confidence interval = 0.615 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
PDE4B	NM_002600.4	c.282-40611C>A		intron_variant		ENST00000341517.9	NP_002591.2

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
PDE4B	ENST00000341517.9	c.282-40611C>A		intron_variant		1	NM_002600.4	ENSP00000342637	A1

Frequencies

GnomAD3 genomes AF: 0.487 AC: 74020 AN: 151844 Hom.: 19140 Cov.: 31

Gnomad AFR AF: 0.299

Gnomad AMI AF: 0.519

Gnomad AMR AF: 0.585

Gnomad ASJ AF: 0.525

Gnomad EAS AF: 0.569

Gnomad SAS AF: 0.633

Gnomad FIN AF: 0.600

Gnomad MID AF: 0.563

Gnomad NFE AF: 0.543

Gnomad OTH AF: 0.483

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

GnomAD4 genome AF: 0.487 AC: 74053 AN: 151962 Hom.: 19150 Cov.: 31 AF XY: 0.493 AC XY: 36646 AN XY: 74266

Gnomad4 AFR AF: 0.299

Gnomad4 AMR AF: 0.586

Gnomad4 ASJ AF: 0.525

Gnomad4 EAS AF: 0.569

Gnomad4 SAS AF: 0.634

Gnomad4 FIN AF: 0.600

Gnomad4 NFE AF: 0.544

Gnomad4 OTH AF: 0.481

Alfa AF: 0.522 Hom.: 3196

Bravo AF: 0.474

Asia WGS AF: 0.584 AC: 2030 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.85
CADD	Benign	4.3
DANN	Benign	0.70

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

Publications

LitVar

Other links and lift over

dbSNP: rs10454453; hg19: chr1-66672532;