rs10493392

chr1-65860000-C-Gchr1-65860000-C-T

Variant summary

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

The NM_002600.4(PDE4B):c.-70-53245C>G variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.135 in 152,096 control chromosomes in the GnomAD database, including 1,455 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 0.13 (1455 hom., cov: 32)
• Consequence: PDE4B NM_002600.4 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -1.24

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=-0.97).
• BA1: GnomAd4 highest subpopulation (SAS) allele frequency at 95% confidence interval = 0.16 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
PDE4B	NM_002600.4	c.-70-53245C>G		intron_variant		ENST00000341517.9
PDE4B	NM_001037341.2	c.-70-53245C>G		intron_variant
PDE4B	NM_001297440.2	c.-107-53245C>G		intron_variant

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
PDE4B	ENST00000341517.9	c.-70-53245C>G		intron_variant		1	NM_002600.4	A1
PDE4B	ENST00000329654.8	c.-70-53245C>G		intron_variant		1		A1

Frequencies

GnomAD3 genomes AF: 0.135 AC: 20483 AN: 151978 Hom.: 1454 Cov.: 32

Gnomad AFR AF: 0.112

Gnomad AMI AF: 0.123

Gnomad AMR AF: 0.137

Gnomad ASJ AF: 0.190

Gnomad EAS AF: 0.170

Gnomad SAS AF: 0.170

Gnomad FIN AF: 0.140

Gnomad MID AF: 0.155

Gnomad NFE AF: 0.139

Gnomad OTH AF: 0.138

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

GnomAD4 genome AF: 0.135 AC: 20488 AN: 152096 Hom.: 1455 Cov.: 32 AF XY: 0.136 AC XY: 10121 AN XY: 74352

Gnomad4 AFR AF: 0.112

Gnomad4 AMR AF: 0.137

Gnomad4 ASJ AF: 0.190

Gnomad4 EAS AF: 0.169

Gnomad4 SAS AF: 0.170

Gnomad4 FIN AF: 0.140

Gnomad4 NFE AF: 0.139

Gnomad4 OTH AF: 0.138

Alfa AF: 0.0809 Hom.: 117

Bravo AF: 0.135

Asia WGS AF: 0.167 AC: 580 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.97
Cadd	Benign	0.25
Dann	Benign	0.66

Splicing

Find out detailed SpliceAI scores and Pangolin per-transcript scores at spliceailookup.broadinstitute.org

Publications

LitVar

Other links and lift over

dbSNP: rs10493392; hg19: chr1-66325683;