rs10158178

Positions:

• chr1-66093490-A-G
• chr1-66093490-A-T

Variant summary

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

The NM_002600.4(PDE4B):​c.282-153970A>G variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.418 in 151,658 control chromosomes in the GnomAD database, including 13,467 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 0.42 (13467 hom., cov: 30)
• Consequence: PDE4B NM_002600.4 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 0.200

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=-0.87).
• BA1: GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.474 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
PDE4B	NM_002600.4	c.282-153970A>G		intron_variant		ENST00000341517.9

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
PDE4B	ENST00000341517.9	c.282-153970A>G		intron_variant		1	NM_002600.4	A1

Frequencies

GnomAD3 genomes AF: 0.418 AC: 63371 AN: 151540 Hom.: 13460 Cov.: 30

Gnomad AFR AF: 0.480

Gnomad AMI AF: 0.454

Gnomad AMR AF: 0.379

Gnomad ASJ AF: 0.458

Gnomad EAS AF: 0.324

Gnomad SAS AF: 0.360

Gnomad FIN AF: 0.347

Gnomad MID AF: 0.453

Gnomad NFE AF: 0.409

Gnomad OTH AF: 0.408

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

GnomAD4 genome AF: 0.418 AC: 63410 AN: 151658 Hom.: 13467 Cov.: 30 AF XY: 0.414 AC XY: 30630 AN XY: 74064

Gnomad4 AFR AF: 0.480

Gnomad4 AMR AF: 0.378

Gnomad4 ASJ AF: 0.458

Gnomad4 EAS AF: 0.324

Gnomad4 SAS AF: 0.361

Gnomad4 FIN AF: 0.347

Gnomad4 NFE AF: 0.409

Gnomad4 OTH AF: 0.409

Alfa AF: 0.414 Hom.: 17578

Bravo AF: 0.423

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.87
CADD	Benign	3.4
DANN	Benign	0.55

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: rs10158178; hg19: chr1-66559173;