1-66180503-T-G

Variant names:

• chr1-66180503-T-G
• rs583018
• NM_002600.4:c.282-66957T>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.282-66957T>G variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.514 in 151,920 control chromosomes in the GnomAD database, including 21,129 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 0.51 (21129 hom., cov: 32)
• Consequence: PDE4B NM_002600.4 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.0530
• Publications: 4 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=-0.95).
• BA1: GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.691 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

Selected	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	PDE4B	NM_002600.4	MANE Select	c.282-66957T>G		intron	N/A	NP_002591.2
	PDE4B	NM_001037341.2		c.282-66957T>G		intron	N/A	NP_001032418.1
	PDE4B	NM_001037340.3		c.237-66957T>G		intron	N/A	NP_001032417.1

Ensembl Transcripts

Selected	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	PDE4B	ENST00000341517.9	TSL:1 MANE Select	c.282-66957T>G		intron	N/A	ENSP00000342637.4
	PDE4B	ENST00000329654.8	TSL:1	c.282-66957T>G		intron	N/A	ENSP00000332116.4
	PDE4B	ENST00000423207.6	TSL:1	c.237-66957T>G		intron	N/A	ENSP00000392947.2

Frequencies

GnomAD3 genomes AF: 0.514 AC: 78082 AN: 151802 Hom.: 21096 Cov.: 32

Gnomad AFR AF: 0.697

Gnomad AMI AF: 0.482

Gnomad AMR AF: 0.424

Gnomad ASJ AF: 0.480

Gnomad EAS AF: 0.457

Gnomad SAS AF: 0.368

Gnomad FIN AF: 0.405

Gnomad MID AF: 0.437

Gnomad NFE AF: 0.457

Gnomad OTH AF: 0.520

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

GnomAD4 genome AF: 0.514 AC: 78162 AN: 151920 Hom.: 21129 Cov.: 32 AF XY: 0.509 AC XY: 37776 AN XY: 74230

African (AFR) AF: 0.698 AC: 28932 AN: 41456

American (AMR) AF: 0.423 AC: 6456 AN: 15272

Ashkenazi Jewish (ASJ) AF: 0.480 AC: 1663 AN: 3468

East Asian (EAS) AF: 0.457 AC: 2356 AN: 5158

South Asian (SAS) AF: 0.367 AC: 1769 AN: 4818

European-Finnish (FIN) AF: 0.405 AC: 4262 AN: 10530

Middle Eastern (MID) AF: 0.422 AC: 124 AN: 294

European-Non Finnish (NFE) AF: 0.457 AC: 31066 AN: 67914

Other (OTH) AF: 0.521 AC: 1098 AN: 2106

Alfa AF: 0.483 Hom.: 5029

Bravo AF: 0.528

Asia WGS AF: 0.415 AC: 1447 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.95
CADD	Benign	1.7
DANN	Benign	0.79
PhyloP100		-0.053
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: rs583018; hg19: chr1-66646186;