rs4457053

Variant names:

• chr5-77129124-G-A
• rs4457053
• ENST00000646262.1:c.-34+10603G>A

Your query was ambiguous. Multiple possible variants found:

• chr5-77129124-G-A
• chr5-77129124-G-T

Variant summary

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

The ENST00000646262.1(PDE8B):​c.-34+10603G>A variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.743 in 151,998 control chromosomes in the GnomAD database, including 42,433 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 0.74 (42433 hom., cov: 30)
• Consequence: PDE8B ENST00000646262.1 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.291
• Publications: 129 publications found

Genes affected

PDE8B (HGNC:):

ZBED3-AS1 (HGNC:44188): (ZBED3 antisense RNA 1)

PDE8B (HGNC:8794): (phosphodiesterase 8B) The protein encoded by this gene is a cyclic nucleotide phosphodiesterase (PDE) that catalyzes the hydrolysis of the second messenger cAMP. The encoded protein, which does not hydrolyze cGMP, is resistant to several PDE inhibitors. Defects in this gene are a cause of autosomal dominant striatal degeneration (ADSD). Several transcript variants encoding different isoforms have been found for this gene.[provided by RefSeq, Jul 2010]

PDE8B Gene-Disease associations (from GenCC):

• autosomal dominant striatal neurodegeneration type 1

  Inheritance: AD Classification: STRONG Submitted by: Ambry Genetics, Labcorp Genetics (formerly Invitae)
• pigmented nodular adrenocortical disease, primary, 3

  Inheritance: AD Classification: STRONG, LIMITED Submitted by: Genomics England PanelApp, Labcorp Genetics (formerly Invitae)
• primary pigmented nodular adrenocortical disease

  Inheritance: AD Classification: SUPPORTIVE Submitted by: Orphanet
• striatal degeneration, autosomal dominant

  Inheritance: AD Classification: SUPPORTIVE Submitted by: Orphanet
• schizophrenia

  Inheritance: Unknown Classification: NO_KNOWN Submitted by: Labcorp Genetics (formerly Invitae)

ACMG classification

Our verdict: Benign. The variant received -12 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.9).
• BA1: GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.926 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
PDE8B	NM_001414622.1	c.-34+10603G>A		intron_variant	Intron 2 of 22		NP_001401551.1
PDE8B	NM_001414623.1	c.-34+10603G>A		intron_variant	Intron 3 of 23		NP_001401552.1
ZBED3-AS1	NR_024398.2	n.525+10603G>A		intron_variant	Intron 3 of 3

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
PDE8B	ENST00000646262.1	c.-34+10603G>A		intron_variant	Intron 3 of 23			ENSP00000493971.1
ENSG00000285000	ENST00000646704.1	n.*85+10603G>A		intron_variant	Intron 14 of 15			ENSP00000495089.1

Frequencies

GnomAD3 genomes AF: 0.743 AC: 112882 AN: 151880 Hom.: 42392 Cov.: 30

Gnomad AFR AF: 0.817

Gnomad AMI AF: 0.765

Gnomad AMR AF: 0.675

Gnomad ASJ AF: 0.626

Gnomad EAS AF: 0.949

Gnomad SAS AF: 0.788

Gnomad FIN AF: 0.781

Gnomad MID AF: 0.665

Gnomad NFE AF: 0.696

Gnomad OTH AF: 0.713

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

GnomAD4 genome AF: 0.743 AC: 112980 AN: 151998 Hom.: 42433 Cov.: 30 AF XY: 0.749 AC XY: 55609 AN XY: 74264

African (AFR) AF: 0.817 AC: 33879 AN: 41474

American (AMR) AF: 0.675 AC: 10299 AN: 15264

Ashkenazi Jewish (ASJ) AF: 0.626 AC: 2170 AN: 3468

East Asian (EAS) AF: 0.948 AC: 4898 AN: 5164

South Asian (SAS) AF: 0.789 AC: 3788 AN: 4802

European-Finnish (FIN) AF: 0.781 AC: 8227 AN: 10538

Middle Eastern (MID) AF: 0.650 AC: 191 AN: 294

European-Non Finnish (NFE) AF: 0.696 AC: 47323 AN: 67980

Other (OTH) AF: 0.717 AC: 1509 AN: 2104

Alfa AF: 0.708 Hom.: 112977

Bravo AF: 0.735

Asia WGS AF: 0.858 AC: 2980 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.90
CADD	Benign	0.86
DANN	Benign	0.53
PhyloP100		-0.29

Splicing

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

Other links and lift over

dbSNP: rs4457053; hg19: chr5-76424949;