rs2180335

Variant names:

• chr1-66320247-A-G
• rs2180335
• NM_002600.4:c.635-12261A>G

Variant summary

Our verdict is Benign. The variant received -12 ACMG points: 0P and 12B. BP4_Strong BA1

The NM_002600.4(PDE4B):​c.635-12261A>G variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.474 in 151,750 control chromosomes in the GnomAD database, including 18,414 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 0.47 (18414 hom., cov: 31)
• Consequence: PDE4B NM_002600.4 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 0.295
• Publications: 8 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=-0.91).
• BA1: GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.794 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
PDE4B	NM_002600.4	c.635-12261A>G		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.635-12261A>G		intron_variant	Intron 7 of 16	1	NM_002600.4	ENSP00000342637.4
PDE4B	ENST00000329654.8	c.635-12261A>G		intron_variant	Intron 7 of 16	1		ENSP00000332116.4
PDE4B	ENST00000423207.6	c.590-12261A>G		intron_variant	Intron 5 of 14	1		ENSP00000392947.2
PDE4B	ENST00000412480.6	c.359-12261A>G		intron_variant	Intron 5 of 5	4		ENSP00000397548.2

Frequencies

GnomAD3 genomes AF: 0.474 AC: 71898 AN: 151632 Hom.: 18408 Cov.: 31

Gnomad AFR AF: 0.275

Gnomad AMI AF: 0.675

Gnomad AMR AF: 0.545

Gnomad ASJ AF: 0.608

Gnomad EAS AF: 0.815

Gnomad SAS AF: 0.533

Gnomad FIN AF: 0.513

Gnomad MID AF: 0.589

Gnomad NFE AF: 0.532

Gnomad OTH AF: 0.501

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

GnomAD4 genome AF: 0.474 AC: 71937 AN: 151750 Hom.: 18414 Cov.: 31 AF XY: 0.477 AC XY: 35384 AN XY: 74108

African (AFR) AF: 0.275 AC: 11395 AN: 41394

American (AMR) AF: 0.546 AC: 8312 AN: 15214

Ashkenazi Jewish (ASJ) AF: 0.608 AC: 2109 AN: 3468

East Asian (EAS) AF: 0.815 AC: 4190 AN: 5142

South Asian (SAS) AF: 0.533 AC: 2566 AN: 4818

European-Finnish (FIN) AF: 0.513 AC: 5375 AN: 10470

Middle Eastern (MID) AF: 0.578 AC: 170 AN: 294

European-Non Finnish (NFE) AF: 0.532 AC: 36157 AN: 67932

Other (OTH) AF: 0.498 AC: 1049 AN: 2108

Alfa AF: 0.523 Hom.: 11632

Bravo AF: 0.471

Asia WGS AF: 0.608 AC: 2109 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.91
CADD	Benign	3.8
DANN	Benign	0.59
PhyloP100		0.29
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: rs2180335; hg19: chr1-66785930;