1-66357451-G-T

Variant names:

• chr1-66357451-G-T
• rs2144719
• NM_002600.4:c.841+1831G>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.841+1831G>T variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.708 in 151,782 control chromosomes in the GnomAD database, including 39,479 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 0.71 (39479 hom., cov: 30)
• Consequence: PDE4B NM_002600.4 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 0.359
• Publications: 7 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 = 0.895 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
PDE4B	NM_002600.4	c.841+1831G>T		intron_variant	Intron 9 of 16	ENST00000341517.9	NP_002591.2

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
PDE4B	ENST00000341517.9	c.841+1831G>T		intron_variant	Intron 9 of 16	1	NM_002600.4	ENSP00000342637.4

Frequencies

GnomAD3 genomes AF: 0.707 AC: 107301 AN: 151664 Hom.: 39421 Cov.: 30

Gnomad AFR AF: 0.895

Gnomad AMI AF: 0.719

Gnomad AMR AF: 0.680

Gnomad ASJ AF: 0.676

Gnomad EAS AF: 0.917

Gnomad SAS AF: 0.817

Gnomad FIN AF: 0.553

Gnomad MID AF: 0.744

Gnomad NFE AF: 0.601

Gnomad OTH AF: 0.709

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

GnomAD4 genome AF: 0.708 AC: 107416 AN: 151782 Hom.: 39479 Cov.: 30 AF XY: 0.710 AC XY: 52605 AN XY: 74114

African (AFR) AF: 0.896 AC: 37120 AN: 41448

American (AMR) AF: 0.681 AC: 10382 AN: 15244

Ashkenazi Jewish (ASJ) AF: 0.676 AC: 2347 AN: 3470

East Asian (EAS) AF: 0.917 AC: 4706 AN: 5132

South Asian (SAS) AF: 0.816 AC: 3932 AN: 4818

European-Finnish (FIN) AF: 0.553 AC: 5758 AN: 10418

Middle Eastern (MID) AF: 0.745 AC: 219 AN: 294

European-Non Finnish (NFE) AF: 0.600 AC: 40795 AN: 67936

Other (OTH) AF: 0.712 AC: 1503 AN: 2112

Alfa AF: 0.646 Hom.: 96349

Bravo AF: 0.725

Asia WGS AF: 0.866 AC: 3011 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	2.2
DANN	Benign	0.54
PhyloP100		0.36
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: rs2144719; hg19: chr1-66823134;