chr1-66169688-T-C

Variant names:

• chr1-66169688-T-C
• rs2069278
• NM_002600.4:c.282-77772T>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.282-77772T>C variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.467 in 152,040 control chromosomes in the GnomAD database, including 19,183 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 (19183 hom., cov: 32)
• Consequence: PDE4B NM_002600.4 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -1.75
• Publications: 6 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 (AFR) allele frequency at 95% confidence interval = 0.721 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
PDE4B	NM_002600.4	c.282-77772T>C		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.282-77772T>C		intron_variant	Intron 3 of 16	1	NM_002600.4	ENSP00000342637.4

Frequencies

GnomAD3 genomes AF: 0.466 AC: 70862 AN: 151924 Hom.: 19138 Cov.: 32

Gnomad AFR AF: 0.727

Gnomad AMI AF: 0.191

Gnomad AMR AF: 0.458

Gnomad ASJ AF: 0.303

Gnomad EAS AF: 0.660

Gnomad SAS AF: 0.491

Gnomad FIN AF: 0.399

Gnomad MID AF: 0.354

Gnomad NFE AF: 0.317

Gnomad OTH AF: 0.450

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

GnomAD4 genome AF: 0.467 AC: 70974 AN: 152040 Hom.: 19183 Cov.: 32 AF XY: 0.471 AC XY: 34971 AN XY: 74302

African (AFR) AF: 0.727 AC: 30162 AN: 41464

American (AMR) AF: 0.459 AC: 7012 AN: 15266

Ashkenazi Jewish (ASJ) AF: 0.303 AC: 1050 AN: 3470

East Asian (EAS) AF: 0.660 AC: 3410 AN: 5164

South Asian (SAS) AF: 0.490 AC: 2364 AN: 4824

European-Finnish (FIN) AF: 0.399 AC: 4223 AN: 10586

Middle Eastern (MID) AF: 0.347 AC: 102 AN: 294

European-Non Finnish (NFE) AF: 0.317 AC: 21525 AN: 67950

Other (OTH) AF: 0.451 AC: 952 AN: 2110

Alfa AF: 0.366 Hom.: 6552

Bravo AF: 0.485

Asia WGS AF: 0.594 AC: 2062 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.90
CADD	Benign	0.49
DANN	Benign	0.61
PhyloP100		-1.7
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: rs2069278; hg19: chr1-66635371; COSMIC: COSV58471294;