NM_003719.5:c.339+46020G>A

Variant names:

• chr5-77257284-G-A
• rs251429
• NM_003719.5:c.339+46020G>A

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+46020G>A variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.686 in 151,956 control chromosomes in the GnomAD database, including 36,122 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 0.69 (36122 hom., cov: 32)
• Consequence: PDE8B NM_003719.5 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.0570
• Publications: 1 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 = 0.929 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
PDE8B	NM_003719.5	c.339+46020G>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+46020G>A		intron_variant	Intron 1 of 21	1	NM_003719.5	ENSP00000264917.6
PDE8B	ENST00000646262.1	c.-33-54710G>A		intron_variant	Intron 3 of 23			ENSP00000493971.1

Frequencies

GnomAD3 genomes AF: 0.686 AC: 104149 AN: 151840 Hom.: 36084 Cov.: 32

Gnomad AFR AF: 0.731

Gnomad AMI AF: 0.499

Gnomad AMR AF: 0.714

Gnomad ASJ AF: 0.588

Gnomad EAS AF: 0.951

Gnomad SAS AF: 0.793

Gnomad FIN AF: 0.686

Gnomad MID AF: 0.623

Gnomad NFE AF: 0.632

Gnomad OTH AF: 0.696

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

GnomAD4 genome AF: 0.686 AC: 104249 AN: 151956 Hom.: 36122 Cov.: 32 AF XY: 0.691 AC XY: 51347 AN XY: 74260

African (AFR) AF: 0.731 AC: 30299 AN: 41450

American (AMR) AF: 0.714 AC: 10906 AN: 15280

Ashkenazi Jewish (ASJ) AF: 0.588 AC: 2033 AN: 3460

East Asian (EAS) AF: 0.951 AC: 4923 AN: 5176

South Asian (SAS) AF: 0.794 AC: 3828 AN: 4824

European-Finnish (FIN) AF: 0.686 AC: 7234 AN: 10540

Middle Eastern (MID) AF: 0.612 AC: 180 AN: 294

European-Non Finnish (NFE) AF: 0.632 AC: 42919 AN: 67916

Other (OTH) AF: 0.699 AC: 1473 AN: 2106

Alfa AF: 0.663 Hom.: 4342

Bravo AF: 0.686

Asia WGS AF: 0.870 AC: 3011 AN: 3462

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.92
CADD	Benign	1.2
DANN	Benign	0.27
PhyloP100		-0.057
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: rs251429; hg19: chr5-76553109;