chr1-66183419-T-C

Variant names:

• chr1-66183419-T-C
• rs526772
• NM_002600.4:c.282-64041T>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.282-64041T>C variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.127 in 152,210 control chromosomes in the GnomAD database, including 1,432 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 0.13 (1432 hom., cov: 32)
• Consequence: PDE4B NM_002600.4 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 0.0550
• Publications: 2 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=-0.82).
• BA1: GnomAd4 highest subpopulation (NFE) allele frequency at 95% confidence interval = 0.163 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
PDE4B	NM_002600.4	c.282-64041T>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.282-64041T>C		intron_variant	Intron 3 of 16	1	NM_002600.4	ENSP00000342637.4

Frequencies

GnomAD3 genomes AF: 0.127 AC: 19360 AN: 152092 Hom.: 1433 Cov.: 32

Gnomad AFR AF: 0.0624

Gnomad AMI AF: 0.205

Gnomad AMR AF: 0.108

Gnomad ASJ AF: 0.120

Gnomad EAS AF: 0.140

Gnomad SAS AF: 0.0435

Gnomad FIN AF: 0.187

Gnomad MID AF: 0.0823

Gnomad NFE AF: 0.166

Gnomad OTH AF: 0.139

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

GnomAD4 genome AF: 0.127 AC: 19357 AN: 152210 Hom.: 1432 Cov.: 32 AF XY: 0.127 AC XY: 9457 AN XY: 74404

African (AFR) AF: 0.0622 AC: 2587 AN: 41560

American (AMR) AF: 0.108 AC: 1645 AN: 15266

Ashkenazi Jewish (ASJ) AF: 0.120 AC: 418 AN: 3470

East Asian (EAS) AF: 0.140 AC: 726 AN: 5182

South Asian (SAS) AF: 0.0431 AC: 208 AN: 4828

European-Finnish (FIN) AF: 0.187 AC: 1977 AN: 10582

Middle Eastern (MID) AF: 0.0816 AC: 24 AN: 294

European-Non Finnish (NFE) AF: 0.166 AC: 11292 AN: 68004

Other (OTH) AF: 0.139 AC: 293 AN: 2112

Alfa AF: 0.146 Hom.: 2457

Bravo AF: 0.120

Asia WGS AF: 0.0980 AC: 341 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.82
CADD	Benign	8.0
DANN	Benign	0.60
PhyloP100		0.055
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: rs526772; hg19: chr1-66649102;