rs4353064

Variant names:

• chr1-65891992-A-C
• rs4353064
• NM_002600.4:c.-70-21253A>C

Variant summary

Our verdict is Benign. The variant received -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
• Publications: 4 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=-0.67).
• 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 rank	MANE	Protein	UniProt
PDE4B	NM_002600.4	c.-70-21253A>C		intron_variant	Intron 1 of 16	ENST00000341517.9	NP_002591.2
PDE4B	NM_001037341.2	c.-70-21253A>C		intron_variant	Intron 1 of 16		NP_001032418.1
PDE4B	NM_001297440.2	c.-107-21253A>C		intron_variant	Intron 1 of 15		NP_001284369.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
PDE4B	ENST00000341517.9	c.-70-21253A>C		intron_variant	Intron 1 of 16	1	NM_002600.4	ENSP00000342637.4
PDE4B	ENST00000329654.8	c.-70-21253A>C		intron_variant	Intron 1 of 16	1		ENSP00000332116.4

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

African (AFR) AF: 0.0845 AC: 3504 AN: 41484

American (AMR) AF: 0.224 AC: 3406 AN: 15214

Ashkenazi Jewish (ASJ) AF: 0.266 AC: 922 AN: 3468

East Asian (EAS) AF: 0.374 AC: 1931 AN: 5168

South Asian (SAS) AF: 0.382 AC: 1835 AN: 4804

European-Finnish (FIN) AF: 0.148 AC: 1564 AN: 10566

Middle Eastern (MID) AF: 0.238 AC: 70 AN: 294

European-Non Finnish (NFE) AF: 0.204 AC: 13834 AN: 67886

Other (OTH) AF: 0.195 AC: 411 AN: 2108

Alfa AF: 0.207 Hom.: 1998

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
PhyloP100		-0.71
Mutation Taster		=100/0	polymorphism (auto)

Splicing

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

Other links and lift over

dbSNP: rs4353064; hg19: chr1-66357675;