rs1937443

Variant names:

• chr1-66003960-C-G
• rs1937443
• NM_002600.4:c.281+85125C>G

Variant summary

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

The NM_002600.4(PDE4B):​c.281+85125C>G variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.572 in 152,020 control chromosomes in the GnomAD database, including 25,113 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 0.57 (25113 hom., cov: 33)
• Consequence: PDE4B NM_002600.4 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.0770
• Publications: 7 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=-0.85).
• BA1: GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.616 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
PDE4B	NM_002600.4	c.281+85125C>G		intron_variant	Intron 3 of 16	ENST00000341517.9	NP_002591.2

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
PDE4B	ENST00000341517.9	c.281+85125C>G		intron_variant	Intron 3 of 16	1	NM_002600.4	ENSP00000342637.4

Frequencies

GnomAD3 genomes AF: 0.572 AC: 86958 AN: 151902 Hom.: 25087 Cov.: 33

Gnomad AFR AF: 0.622

Gnomad AMI AF: 0.577

Gnomad AMR AF: 0.540

Gnomad ASJ AF: 0.466

Gnomad EAS AF: 0.469

Gnomad SAS AF: 0.430

Gnomad FIN AF: 0.626

Gnomad MID AF: 0.427

Gnomad NFE AF: 0.566

Gnomad OTH AF: 0.547

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

GnomAD4 genome AF: 0.572 AC: 87027 AN: 152020 Hom.: 25113 Cov.: 33 AF XY: 0.573 AC XY: 42550 AN XY: 74300

African (AFR) AF: 0.622 AC: 25810 AN: 41474

American (AMR) AF: 0.540 AC: 8228 AN: 15246

Ashkenazi Jewish (ASJ) AF: 0.466 AC: 1618 AN: 3470

East Asian (EAS) AF: 0.469 AC: 2429 AN: 5180

South Asian (SAS) AF: 0.430 AC: 2075 AN: 4824

European-Finnish (FIN) AF: 0.626 AC: 6608 AN: 10562

Middle Eastern (MID) AF: 0.429 AC: 126 AN: 294

European-Non Finnish (NFE) AF: 0.566 AC: 38467 AN: 67952

Other (OTH) AF: 0.541 AC: 1142 AN: 2110

Alfa AF: 0.573 Hom.: 3154

Bravo AF: 0.570

Asia WGS AF: 0.394 AC: 1372 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	1.5
DANN	Benign	0.44
PhyloP100		-0.077
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: rs1937443; hg19: chr1-66469643;