1-66055315-A-G

Variant names:

• chr1-66055315-A-G
• rs2455012
• NM_002600.4:c.281+136480A>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.281+136480A>G variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.959 in 152,314 control chromosomes in the GnomAD database, including 70,007 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 0.96 (70007 hom., cov: 33)
• Consequence: PDE4B NM_002600.4 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 0.611
• Publications: 10 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 = 0.956 is higher than 0.05.

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_002600.4. You can select a different transcript below to see updated ACMG assignments.

RefSeq Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	PDE4B	NM_002600.4	MANE Select	c.281+136480A>G		intron	N/A	NP_002591.2
	PDE4B	NM_001037341.2		c.281+136480A>G		intron	N/A	NP_001032418.1	X5DNX5
	PDE4B	NM_001037340.3		c.236+62173A>G		intron	N/A	NP_001032417.1	Q07343-3

Ensembl Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	PDE4B	ENST00000341517.9	TSL:1 MANE Select	c.281+136480A>G		intron	N/A	ENSP00000342637.4	Q07343-1
	PDE4B	ENST00000329654.8	TSL:1	c.281+136480A>G		intron	N/A	ENSP00000332116.4	Q07343-1
	PDE4B	ENST00000423207.6	TSL:1	c.236+62173A>G		intron	N/A	ENSP00000392947.2	Q07343-3

Frequencies

GnomAD3 genomes AF: 0.959 AC: 145897 AN: 152196 Hom.: 69954 Cov.: 33

Gnomad AFR AF: 0.958

Gnomad AMI AF: 0.946

Gnomad AMR AF: 0.966

Gnomad ASJ AF: 0.937

Gnomad EAS AF: 0.979

Gnomad SAS AF: 0.970

Gnomad FIN AF: 0.986

Gnomad MID AF: 0.962

Gnomad NFE AF: 0.952

Gnomad OTH AF: 0.963

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

GnomAD4 genome AF: 0.959 AC: 146009 AN: 152314 Hom.: 70007 Cov.: 33 AF XY: 0.960 AC XY: 71534 AN XY: 74476

African (AFR) AF: 0.958 AC: 39830 AN: 41572

American (AMR) AF: 0.966 AC: 14781 AN: 15300

Ashkenazi Jewish (ASJ) AF: 0.937 AC: 3253 AN: 3472

East Asian (EAS) AF: 0.979 AC: 5073 AN: 5184

South Asian (SAS) AF: 0.969 AC: 4669 AN: 4816

European-Finnish (FIN) AF: 0.986 AC: 10477 AN: 10624

Middle Eastern (MID) AF: 0.966 AC: 284 AN: 294

European-Non Finnish (NFE) AF: 0.952 AC: 64744 AN: 68026

Other (OTH) AF: 0.963 AC: 2035 AN: 2114

Alfa AF: 0.952 Hom.: 96423

Bravo AF: 0.957

Asia WGS AF: 0.957 AC: 3327 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.91
CADD	Benign	3.4
DANN	Benign	0.35
PhyloP100		0.61
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: rs2455012; hg19: chr1-66520998;