5-77226043-T-C

Variant names:

• chr5-77226043-T-C
• rs1382879
• NM_003719.5:c.339+14779T>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+14779T>C variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.547 in 152,106 control chromosomes in the GnomAD database, including 25,433 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 0.55 (25433 hom., cov: 32)
• Consequence: PDE8B NM_003719.5 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 0.0230
• Publications: 13 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=-0.97).
• BA1: GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.813 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
PDE8B	NM_003719.5	c.339+14779T>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+14779T>C		intron_variant	Intron 1 of 21	1	NM_003719.5	ENSP00000264917.6
PDE8B	ENST00000646262.1	c.-33-85951T>C		intron_variant	Intron 3 of 23			ENSP00000493971.1

Frequencies

GnomAD3 genomes AF: 0.547 AC: 83134 AN: 151988 Hom.: 25378 Cov.: 32

Gnomad AFR AF: 0.811

Gnomad AMI AF: 0.351

Gnomad AMR AF: 0.557

Gnomad ASJ AF: 0.420

Gnomad EAS AF: 0.834

Gnomad SAS AF: 0.563

Gnomad FIN AF: 0.411

Gnomad MID AF: 0.411

Gnomad NFE AF: 0.392

Gnomad OTH AF: 0.545

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

GnomAD4 genome AF: 0.547 AC: 83250 AN: 152106 Hom.: 25433 Cov.: 32 AF XY: 0.548 AC XY: 40784 AN XY: 74362

African (AFR) AF: 0.812 AC: 33700 AN: 41518

American (AMR) AF: 0.556 AC: 8502 AN: 15280

Ashkenazi Jewish (ASJ) AF: 0.420 AC: 1458 AN: 3468

East Asian (EAS) AF: 0.834 AC: 4308 AN: 5164

South Asian (SAS) AF: 0.563 AC: 2718 AN: 4824

European-Finnish (FIN) AF: 0.411 AC: 4341 AN: 10564

Middle Eastern (MID) AF: 0.401 AC: 118 AN: 294

European-Non Finnish (NFE) AF: 0.392 AC: 26625 AN: 67968

Other (OTH) AF: 0.549 AC: 1160 AN: 2114

Alfa AF: 0.435 Hom.: 39853

Bravo AF: 0.570

Asia WGS AF: 0.687 AC: 2390 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	4.8
DANN	Benign	0.82
PhyloP100		0.023
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: rs1382879; hg19: chr5-76521868;