rs4353064

Positions:

• chr1-65891992-A-C

Variant summary

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

The NM_002600.4(PDE4B):​c.-70-21253A>C variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.182 in 151,904 control chromosomes in the GnomAD database, including 2,975 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 0.18 (2975 hom., cov: 32)
• Consequence: PDE4B NM_002600.4 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.712

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=-0.67).
• BA1: GnomAd4 highest subpopulation (SAS) allele frequency at 95% confidence interval = 0.367 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
PDE4B	NM_002600.4	c.-70-21253A>C		intron_variant		ENST00000341517.9
PDE4B	NM_001037341.2	c.-70-21253A>C		intron_variant
PDE4B	NM_001297440.2	c.-107-21253A>C		intron_variant

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
PDE4B	ENST00000341517.9	c.-70-21253A>C		intron_variant		1	NM_002600.4	A1
PDE4B	ENST00000329654.8	c.-70-21253A>C		intron_variant		1		A1

Frequencies

GnomAD3 genomes AF: 0.182 AC: 27669 AN: 151786 Hom.: 2975 Cov.: 32

Gnomad AFR AF: 0.0844

Gnomad AMI AF: 0.221

Gnomad AMR AF: 0.224

Gnomad ASJ AF: 0.266

Gnomad EAS AF: 0.372

Gnomad SAS AF: 0.383

Gnomad FIN AF: 0.148

Gnomad MID AF: 0.247

Gnomad NFE AF: 0.204

Gnomad OTH AF: 0.195

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

GnomAD4 genome AF: 0.182 AC: 27679 AN: 151904 Hom.: 2975 Cov.: 32 AF XY: 0.186 AC XY: 13778 AN XY: 74228

Gnomad4 AFR AF: 0.0845

Gnomad4 AMR AF: 0.224

Gnomad4 ASJ AF: 0.266

Gnomad4 EAS AF: 0.374

Gnomad4 SAS AF: 0.382

Gnomad4 FIN AF: 0.148

Gnomad4 NFE AF: 0.204

Gnomad4 OTH AF: 0.195

Alfa AF: 0.207 Hom.: 1848

Bravo AF: 0.181

Asia WGS AF: 0.407 AC: 1405 AN: 3466

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.67
CADD	Benign	9.6
DANN	Benign	0.87

Splicing

Find out detailed SpliceAI scores and Pangolin per-transcript scores at spliceailookup.broadinstitute.org

Publications

LitVar

Other links and lift over

dbSNP: rs4353064; hg19: chr1-66357675;