rs12060491

Positions:

• chr1-66279669-A-G
• chr1-66279669-A-T

Variant summary

Our verdict is Benign. Variant got -12 ACMG points: 0P and 12B. BP4_Strong BA1

The NM_002600.4(PDE4B):​c.634+13582A>G variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.205 in 152,184 control chromosomes in the GnomAD database, including 3,685 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 0.20 (3685 hom., cov: 32)
• Consequence: PDE4B NM_002600.4 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 0.572

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

Verdict is Benign. Variant got -12 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.89).
• BA1: GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.398 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
PDE4B	NM_002600.4	c.634+13582A>G		intron_variant		ENST00000341517.9	NP_002591.2

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
PDE4B	ENST00000341517.9	c.634+13582A>G		intron_variant		1	NM_002600.4	ENSP00000342637	A1
PDE4B	ENST00000329654.8	c.634+13582A>G		intron_variant		1		ENSP00000332116	A1
PDE4B	ENST00000423207.6	c.589+13582A>G		intron_variant		1		ENSP00000392947	P3
PDE4B	ENST00000412480.6	c.358+13582A>G		intron_variant		4		ENSP00000397548

Frequencies

GnomAD3 genomes AF: 0.205 AC: 31167 AN: 152066 Hom.: 3678 Cov.: 32

Gnomad AFR AF: 0.198

Gnomad AMI AF: 0.128

Gnomad AMR AF: 0.310

Gnomad ASJ AF: 0.174

Gnomad EAS AF: 0.413

Gnomad SAS AF: 0.363

Gnomad FIN AF: 0.165

Gnomad MID AF: 0.244

Gnomad NFE AF: 0.167

Gnomad OTH AF: 0.207

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

GnomAD4 genome AF: 0.205 AC: 31197 AN: 152184 Hom.: 3685 Cov.: 32 AF XY: 0.211 AC XY: 15718 AN XY: 74410

Gnomad4 AFR AF: 0.197

Gnomad4 AMR AF: 0.312

Gnomad4 ASJ AF: 0.174

Gnomad4 EAS AF: 0.412

Gnomad4 SAS AF: 0.363

Gnomad4 FIN AF: 0.165

Gnomad4 NFE AF: 0.167

Gnomad4 OTH AF: 0.208

Alfa AF: 0.182 Hom.: 3633

Bravo AF: 0.211

Asia WGS AF: 0.389 AC: 1354 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.89
CADD	Benign	5.0
DANN	Benign	0.70

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

Publications

LitVar

Other links and lift over

dbSNP: rs12060491; hg19: chr1-66745352;