rs1321177

Variant names:

• chr1-66349388-G-T
• rs1321177
• NM_002600.4:c.748-6139G>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.748-6139G>T variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.689 in 152,024 control chromosomes in the GnomAD database, including 36,305 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 0.69 (36305 hom., cov: 31)
• Consequence: PDE4B NM_002600.4 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 0.104
• Publications: 5 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=-0.85).
• BA1: GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.872 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
PDE4B	NM_002600.4	c.748-6139G>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.748-6139G>T		intron_variant	Intron 8 of 16	1	NM_002600.4	ENSP00000342637.4

Frequencies

GnomAD3 genomes AF: 0.689 AC: 104631 AN: 151906 Hom.: 36283 Cov.: 31

Gnomad AFR AF: 0.696

Gnomad AMI AF: 0.759

Gnomad AMR AF: 0.684

Gnomad ASJ AF: 0.713

Gnomad EAS AF: 0.894

Gnomad SAS AF: 0.746

Gnomad FIN AF: 0.631

Gnomad MID AF: 0.794

Gnomad NFE AF: 0.672

Gnomad OTH AF: 0.702

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

GnomAD4 genome AF: 0.689 AC: 104702 AN: 152024 Hom.: 36305 Cov.: 31 AF XY: 0.689 AC XY: 51207 AN XY: 74284

African (AFR) AF: 0.696 AC: 28849 AN: 41462

American (AMR) AF: 0.684 AC: 10440 AN: 15256

Ashkenazi Jewish (ASJ) AF: 0.713 AC: 2475 AN: 3472

East Asian (EAS) AF: 0.893 AC: 4621 AN: 5172

South Asian (SAS) AF: 0.746 AC: 3592 AN: 4814

European-Finnish (FIN) AF: 0.631 AC: 6672 AN: 10566

Middle Eastern (MID) AF: 0.789 AC: 232 AN: 294

European-Non Finnish (NFE) AF: 0.672 AC: 45639 AN: 67962

Other (OTH) AF: 0.705 AC: 1490 AN: 2114

Alfa AF: 0.684 Hom.: 54432

Bravo AF: 0.693

Asia WGS AF: 0.798 AC: 2778 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.85
CADD	Benign	1.2
DANN	Benign	0.65
PhyloP100		0.10
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: rs1321177; hg19: chr1-66815071;