5-77244147-T-C

Variant names:

• chr5-77244147-T-C
• rs12515498
• NM_003719.5:c.339+32883T>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+32883T>C variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.328 in 151,670 control chromosomes in the GnomAD database, including 9,137 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 0.33 (9137 hom., cov: 31)
• Consequence: PDE8B NM_003719.5 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.451
• Publications: 7 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=-0.92).
• BA1: GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.809 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
PDE8B	NM_003719.5	c.339+32883T>C		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+32883T>C		intron_variant	Intron 1 of 21	1	NM_003719.5	ENSP00000264917.6
PDE8B	ENST00000646262.1	c.-33-67847T>C		intron_variant	Intron 3 of 23			ENSP00000493971.1

Frequencies

GnomAD3 genomes AF: 0.328 AC: 49690 AN: 151552 Hom.: 9118 Cov.: 31

Gnomad AFR AF: 0.396

Gnomad AMI AF: 0.265

Gnomad AMR AF: 0.310

Gnomad ASJ AF: 0.258

Gnomad EAS AF: 0.830

Gnomad SAS AF: 0.429

Gnomad FIN AF: 0.289

Gnomad MID AF: 0.236

Gnomad NFE AF: 0.256

Gnomad OTH AF: 0.347

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

GnomAD4 genome AF: 0.328 AC: 49750 AN: 151670 Hom.: 9137 Cov.: 31 AF XY: 0.333 AC XY: 24654 AN XY: 74068

African (AFR) AF: 0.396 AC: 16374 AN: 41342

American (AMR) AF: 0.310 AC: 4717 AN: 15234

Ashkenazi Jewish (ASJ) AF: 0.258 AC: 893 AN: 3464

East Asian (EAS) AF: 0.830 AC: 4239 AN: 5110

South Asian (SAS) AF: 0.430 AC: 2065 AN: 4802

European-Finnish (FIN) AF: 0.289 AC: 3042 AN: 10522

Middle Eastern (MID) AF: 0.223 AC: 65 AN: 292

European-Non Finnish (NFE) AF: 0.256 AC: 17372 AN: 67894

Other (OTH) AF: 0.353 AC: 743 AN: 2106

Alfa AF: 0.284 Hom.: 26909

Bravo AF: 0.336

Asia WGS AF: 0.592 AC: 2054 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.92
CADD	Benign	0.35
DANN	Benign	0.36
PhyloP100		-0.45
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: rs12515498; hg19: chr5-76539972; COSMIC: COSV53737742;