rs989758

Variant names:

• chr5-77249135-G-A
• rs989758
• NM_003719.5:c.339+37871G>A

Your query was ambiguous. Multiple possible variants found:

• chr5-77249135-G-A
• chr5-77249135-G-C

Variant summary

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

The NM_003719.5(PDE8B):​c.339+37871G>A variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.411 in 152,072 control chromosomes in the GnomAD database, including 13,399 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 0.41 (13399 hom., cov: 33)
• Consequence: PDE8B NM_003719.5 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 0.569
• Publications: 5 publications found

Genes affected

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)

PDE8B (HGNC:):

ACMG classification

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

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.8).
• BA1: GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.731 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
PDE8B	NM_003719.5	c.339+37871G>A		intron_variant	Intron 1 of 21	ENST00000264917.10	NP_003710.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
PDE8B	ENST00000264917.10	c.339+37871G>A		intron_variant	Intron 1 of 21	1	NM_003719.5	ENSP00000264917.6
PDE8B	ENST00000646262.1	c.-33-62859G>A		intron_variant	Intron 3 of 23			ENSP00000493971.1

Frequencies

GnomAD3 genomes AF: 0.411 AC: 62451 AN: 151954 Hom.: 13376 Cov.: 33

Gnomad AFR AF: 0.426

Gnomad AMI AF: 0.303

Gnomad AMR AF: 0.493

Gnomad ASJ AF: 0.404

Gnomad EAS AF: 0.751

Gnomad SAS AF: 0.498

Gnomad FIN AF: 0.374

Gnomad MID AF: 0.323

Gnomad NFE AF: 0.359

Gnomad OTH AF: 0.420

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

GnomAD4 genome AF: 0.411 AC: 62529 AN: 152072 Hom.: 13399 Cov.: 33 AF XY: 0.416 AC XY: 30920 AN XY: 74356

African (AFR) AF: 0.427 AC: 17698 AN: 41490

American (AMR) AF: 0.493 AC: 7530 AN: 15284

Ashkenazi Jewish (ASJ) AF: 0.404 AC: 1401 AN: 3470

East Asian (EAS) AF: 0.750 AC: 3879 AN: 5170

South Asian (SAS) AF: 0.498 AC: 2399 AN: 4816

European-Finnish (FIN) AF: 0.374 AC: 3948 AN: 10570

Middle Eastern (MID) AF: 0.316 AC: 93 AN: 294

European-Non Finnish (NFE) AF: 0.359 AC: 24415 AN: 67960

Other (OTH) AF: 0.422 AC: 890 AN: 2108

Alfa AF: 0.378 Hom.: 8101

Bravo AF: 0.418

Asia WGS AF: 0.592 AC: 2060 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.80
CADD	Benign	5.1
DANN	Benign	0.57
PhyloP100		0.57
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: rs989758; hg19: chr5-76544960;