1-66303417-G-C

Variant names:

• chr1-66303417-G-C
• rs6683977
• NM_002600.4:c.635-29091G>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.635-29091G>C variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.392 in 151,296 control chromosomes in the GnomAD database, including 14,916 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 0.39 (14916 hom., cov: 29)
• Consequence: PDE4B NM_002600.4 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.184
• 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=-0.92).
• BA1: GnomAd4 highest subpopulation (NFE) allele frequency at 95% confidence interval = 0.554 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
PDE4B	NM_002600.4	c.635-29091G>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.635-29091G>C		intron_variant	Intron 7 of 16	1	NM_002600.4	ENSP00000342637.4
PDE4B	ENST00000329654.8	c.635-29091G>C		intron_variant	Intron 7 of 16	1		ENSP00000332116.4
PDE4B	ENST00000423207.6	c.590-29091G>C		intron_variant	Intron 5 of 14	1		ENSP00000392947.2
PDE4B	ENST00000412480.6	c.359-29091G>C		intron_variant	Intron 5 of 5	4		ENSP00000397548.2

Frequencies

GnomAD3 genomes AF: 0.392 AC: 59247 AN: 151178 Hom.: 14917 Cov.: 29

Gnomad AFR AF: 0.105

Gnomad AMI AF: 0.581

Gnomad AMR AF: 0.343

Gnomad ASJ AF: 0.517

Gnomad EAS AF: 0.153

Gnomad SAS AF: 0.356

Gnomad FIN AF: 0.588

Gnomad MID AF: 0.389

Gnomad NFE AF: 0.559

Gnomad OTH AF: 0.390

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

GnomAD4 genome AF: 0.392 AC: 59243 AN: 151296 Hom.: 14916 Cov.: 29 AF XY: 0.391 AC XY: 28851 AN XY: 73880

African (AFR) AF: 0.105 AC: 4313 AN: 41270

American (AMR) AF: 0.342 AC: 5197 AN: 15182

Ashkenazi Jewish (ASJ) AF: 0.517 AC: 1788 AN: 3460

East Asian (EAS) AF: 0.153 AC: 787 AN: 5132

South Asian (SAS) AF: 0.359 AC: 1717 AN: 4782

European-Finnish (FIN) AF: 0.588 AC: 6116 AN: 10398

Middle Eastern (MID) AF: 0.394 AC: 115 AN: 292

European-Non Finnish (NFE) AF: 0.559 AC: 37871 AN: 67772

Other (OTH) AF: 0.387 AC: 814 AN: 2104

Alfa AF: 0.470 Hom.: 2326

Bravo AF: 0.359

Asia WGS AF: 0.219 AC: 763 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	0.49
DANN	Benign	0.62
PhyloP100		-0.18
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: rs6683977; hg19: chr1-66769100;