1-66337397-C-T

Variant names:

• chr1-66337397-C-T
• rs1890196
• NM_002600.4:c.747+4777C>T

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+4777C>T variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.452 in 152,044 control chromosomes in the GnomAD database, including 17,119 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 0.45 (17119 hom., cov: 32)
• Consequence: PDE4B NM_002600.4 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -1.91
• Publications: 3 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=-0.92).
• BA1: GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.787 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
PDE4B	NM_002600.4	c.747+4777C>T		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+4777C>T		intron_variant	Intron 8 of 16	1	NM_002600.4	ENSP00000342637.4

Frequencies

GnomAD3 genomes AF: 0.452 AC: 68664 AN: 151926 Hom.: 17123 Cov.: 32

Gnomad AFR AF: 0.242

Gnomad AMI AF: 0.649

Gnomad AMR AF: 0.512

Gnomad ASJ AF: 0.513

Gnomad EAS AF: 0.808

Gnomad SAS AF: 0.455

Gnomad FIN AF: 0.520

Gnomad MID AF: 0.487

Gnomad NFE AF: 0.522

Gnomad OTH AF: 0.478

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

GnomAD4 genome AF: 0.452 AC: 68667 AN: 152044 Hom.: 17119 Cov.: 32 AF XY: 0.455 AC XY: 33829 AN XY: 74314

African (AFR) AF: 0.242 AC: 10035 AN: 41480

American (AMR) AF: 0.513 AC: 7826 AN: 15270

Ashkenazi Jewish (ASJ) AF: 0.513 AC: 1780 AN: 3470

East Asian (EAS) AF: 0.808 AC: 4173 AN: 5166

South Asian (SAS) AF: 0.455 AC: 2192 AN: 4822

European-Finnish (FIN) AF: 0.520 AC: 5483 AN: 10540

Middle Eastern (MID) AF: 0.480 AC: 141 AN: 294

European-Non Finnish (NFE) AF: 0.521 AC: 35445 AN: 67980

Other (OTH) AF: 0.474 AC: 1001 AN: 2112

Alfa AF: 0.487 Hom.: 28990

Bravo AF: 0.447

Asia WGS AF: 0.555 AC: 1926 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.92
CADD	Benign	0.72
DANN	Benign	0.35
PhyloP100		-1.9
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: rs1890196; hg19: chr1-66803080;