1-66296783-T-C

Variant names:

• chr1-66296783-T-C
• rs546784
• NM_002600.4:c.634+30696T>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.634+30696T>C variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.419 in 152,056 control chromosomes in the GnomAD database, including 15,706 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 0.42 (15706 hom., cov: 32)
• Consequence: PDE4B NM_002600.4 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.637
• Publications: 15 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=-0.76).
• BA1: GnomAd4 highest subpopulation (NFE) allele frequency at 95% confidence interval = 0.555 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
PDE4B	NM_002600.4	c.634+30696T>C		intron_variant	Intron 7 of 16	ENST00000341517.9	NP_002591.2

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
PDE4B	ENST00000341517.9	c.634+30696T>C		intron_variant	Intron 7 of 16	1	NM_002600.4	ENSP00000342637.4
PDE4B	ENST00000329654.8	c.634+30696T>C		intron_variant	Intron 7 of 16	1		ENSP00000332116.4
PDE4B	ENST00000423207.6	c.589+30696T>C		intron_variant	Intron 5 of 14	1		ENSP00000392947.2
PDE4B	ENST00000412480.6	c.358+30696T>C		intron_variant	Intron 5 of 5	4		ENSP00000397548.2

Frequencies

GnomAD3 genomes AF: 0.419 AC: 63697 AN: 151938 Hom.: 15706 Cov.: 32

Gnomad AFR AF: 0.199

Gnomad AMI AF: 0.582

Gnomad AMR AF: 0.350

Gnomad ASJ AF: 0.531

Gnomad EAS AF: 0.152

Gnomad SAS AF: 0.363

Gnomad FIN AF: 0.588

Gnomad MID AF: 0.389

Gnomad NFE AF: 0.560

Gnomad OTH AF: 0.401

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

GnomAD4 genome AF: 0.419 AC: 63701 AN: 152056 Hom.: 15706 Cov.: 32 AF XY: 0.417 AC XY: 31009 AN XY: 74318

African (AFR) AF: 0.198 AC: 8236 AN: 41512

American (AMR) AF: 0.349 AC: 5317 AN: 15234

Ashkenazi Jewish (ASJ) AF: 0.531 AC: 1843 AN: 3470

East Asian (EAS) AF: 0.152 AC: 788 AN: 5172

South Asian (SAS) AF: 0.366 AC: 1764 AN: 4820

European-Finnish (FIN) AF: 0.588 AC: 6227 AN: 10582

Middle Eastern (MID) AF: 0.395 AC: 116 AN: 294

European-Non Finnish (NFE) AF: 0.560 AC: 38039 AN: 67948

Other (OTH) AF: 0.398 AC: 840 AN: 2112

Alfa AF: 0.477 Hom.: 23983

Bravo AF: 0.390

Asia WGS AF: 0.230 AC: 800 AN: 3476

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.76
CADD	Benign	4.9
DANN	Benign	0.67
PhyloP100		-0.64
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: rs546784; hg19: chr1-66762466;