rs11208766

chr1-65907223-G-Achr1-65907223-G-C

Variant summary

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

The NM_002600.4(PDE4B):c.-70-6022G>A variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.474 in 151,958 control chromosomes in the GnomAD database, including 17,482 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 0.47 (17482 hom., cov: 32)
• Consequence: PDE4B NM_002600.4 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.731

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=-0.91).
• BA1: GnomAd4 highest subpopulation (SAS) allele frequency at 95% confidence interval = 0.645 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
PDE4B	NM_002600.4	c.-70-6022G>A		intron_variant		ENST00000341517.9
PDE4B	NM_001037341.2	c.-70-6022G>A		intron_variant
PDE4B	NM_001297440.2	c.-107-6022G>A		intron_variant

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
PDE4B	ENST00000341517.9	c.-70-6022G>A		intron_variant		1	NM_002600.4	A1
PDE4B	ENST00000329654.8	c.-70-6022G>A		intron_variant		1		A1

Frequencies

GnomAD3 genomes AF: 0.474 AC: 71989 AN: 151840 Hom.: 17450 Cov.: 32

Gnomad AFR AF: 0.372

Gnomad AMI AF: 0.542

Gnomad AMR AF: 0.553

Gnomad ASJ AF: 0.539

Gnomad EAS AF: 0.589

Gnomad SAS AF: 0.665

Gnomad FIN AF: 0.446

Gnomad MID AF: 0.608

Gnomad NFE AF: 0.495

Gnomad OTH AF: 0.494

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

GnomAD4 genome AF: 0.474 AC: 72070 AN: 151958 Hom.: 17482 Cov.: 32 AF XY: 0.477 AC XY: 35462 AN XY: 74274

Gnomad4 AFR AF: 0.373

Gnomad4 AMR AF: 0.553

Gnomad4 ASJ AF: 0.539

Gnomad4 EAS AF: 0.590

Gnomad4 SAS AF: 0.664

Gnomad4 FIN AF: 0.446

Gnomad4 NFE AF: 0.495

Gnomad4 OTH AF: 0.496

Alfa AF: 0.481 Hom.: 3356

Bravo AF: 0.475

Asia WGS AF: 0.680 AC: 2361 AN: 3476

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.91
Cadd	Benign	0.097
Dann	Benign	0.23

Splicing

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

Publications

LitVar

Other links and lift over

dbSNP: rs11208766; hg19: chr1-66372906;