rs7708285

Variant names:

• chr5-77130042-G-A
• rs7708285
• ENST00000646262.1:c.-34+11521G>A

Your query was ambiguous. Multiple possible variants found:

• chr5-77130042-G-A
• chr5-77130042-G-C

Variant summary

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

The ENST00000646262.1(PDE8B):​c.-34+11521G>A variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.763 in 152,158 control chromosomes in the GnomAD database, including 44,923 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 0.76 (44923 hom., cov: 32)
• Consequence: PDE8B ENST00000646262.1 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 0.928
• Publications: 38 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=-0.87).
• 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+11521G>A		intron_variant	Intron 2 of 22		NP_001401551.1
PDE8B	NM_001414623.1	c.-34+11521G>A		intron_variant	Intron 3 of 23		NP_001401552.1
ZBED3-AS1	NR_024398.2	n.525+11521G>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+11521G>A		intron_variant	Intron 3 of 23			ENSP00000493971.1
ENSG00000285000	ENST00000646704.1	n.*85+11521G>A		intron_variant	Intron 14 of 15			ENSP00000495089.1

Frequencies

GnomAD3 genomes AF: 0.763 AC: 116050 AN: 152040 Hom.: 44878 Cov.: 32

Gnomad AFR AF: 0.862

Gnomad AMI AF: 0.765

Gnomad AMR AF: 0.686

Gnomad ASJ AF: 0.640

Gnomad EAS AF: 0.948

Gnomad SAS AF: 0.819

Gnomad FIN AF: 0.781

Gnomad MID AF: 0.696

Gnomad NFE AF: 0.707

Gnomad OTH AF: 0.731

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

GnomAD4 genome AF: 0.763 AC: 116152 AN: 152158 Hom.: 44923 Cov.: 32 AF XY: 0.768 AC XY: 57175 AN XY: 74404

African (AFR) AF: 0.862 AC: 35806 AN: 41526

American (AMR) AF: 0.685 AC: 10475 AN: 15282

Ashkenazi Jewish (ASJ) AF: 0.640 AC: 2220 AN: 3470

East Asian (EAS) AF: 0.948 AC: 4899 AN: 5168

South Asian (SAS) AF: 0.820 AC: 3951 AN: 4818

European-Finnish (FIN) AF: 0.781 AC: 8269 AN: 10582

Middle Eastern (MID) AF: 0.680 AC: 200 AN: 294

European-Non Finnish (NFE) AF: 0.707 AC: 48083 AN: 67994

Other (OTH) AF: 0.735 AC: 1553 AN: 2114

Alfa AF: 0.725 Hom.: 107672

Bravo AF: 0.756

Asia WGS AF: 0.877 AC: 3047 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.87
CADD	Benign	5.0
DANN	Benign	0.69
PhyloP100		0.93

Splicing

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

Other links and lift over

dbSNP: rs7708285; hg19: chr5-76425867;