1-66341270-T-C

Variant names:

• chr1-66341270-T-C
• rs2788646
• NM_002600.4:c.747+8650T>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.747+8650T>C variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.554 in 151,998 control chromosomes in the GnomAD database, including 24,093 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 0.55 (24093 hom., cov: 32)
• Consequence: PDE4B NM_002600.4 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -2.03
• Publications: 1 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=-0.9).
• BA1: GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.786 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
PDE4B	NM_002600.4	c.747+8650T>C		intron_variant	Intron 8 of 16	ENST00000341517.9	NP_002591.2

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
PDE4B	ENST00000341517.9	c.747+8650T>C		intron_variant	Intron 8 of 16	1	NM_002600.4	ENSP00000342637.4

Frequencies

GnomAD3 genomes AF: 0.554 AC: 84206 AN: 151882 Hom.: 24089 Cov.: 32

Gnomad AFR AF: 0.420

Gnomad AMI AF: 0.690

Gnomad AMR AF: 0.600

Gnomad ASJ AF: 0.562

Gnomad EAS AF: 0.806

Gnomad SAS AF: 0.474

Gnomad FIN AF: 0.601

Gnomad MID AF: 0.611

Gnomad NFE AF: 0.602

Gnomad OTH AF: 0.577

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

GnomAD4 genome AF: 0.554 AC: 84241 AN: 151998 Hom.: 24093 Cov.: 32 AF XY: 0.555 AC XY: 41237 AN XY: 74274

African (AFR) AF: 0.420 AC: 17391 AN: 41450

American (AMR) AF: 0.601 AC: 9184 AN: 15290

Ashkenazi Jewish (ASJ) AF: 0.562 AC: 1949 AN: 3466

East Asian (EAS) AF: 0.806 AC: 4175 AN: 5178

South Asian (SAS) AF: 0.475 AC: 2290 AN: 4826

European-Finnish (FIN) AF: 0.601 AC: 6332 AN: 10528

Middle Eastern (MID) AF: 0.599 AC: 176 AN: 294

European-Non Finnish (NFE) AF: 0.602 AC: 40897 AN: 67942

Other (OTH) AF: 0.577 AC: 1219 AN: 2114

Alfa AF: 0.562 Hom.: 3011

Bravo AF: 0.552

Asia WGS AF: 0.584 AC: 2026 AN: 3474

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.90
CADD	Benign	0.062
DANN	Benign	0.64
PhyloP100		-2.0
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: rs2788646; hg19: chr1-66806953;