5-77210988-C-T

Variant names:

• chr5-77210988-C-T
• rs201411330
• NM_003719.5:c.63C>T

Variant summary

Our verdict is Benign. The variant received -18 ACMG points: 0P and 18B. BP4_Moderate BP6_Very_Strong BS1 BS2

The NM_001349753.2(PDE8B):​c.-307C>T variant causes a 5 prime UTR premature start codon gain change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.000745 in 1,541,786 control chromosomes in the GnomAD database, including 10 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★★).

• Frequency:
  • Genomes: 𝑓 0.0040 (8 hom., cov: 32)
  • Exomes 𝑓: 0.00039 (2 hom.)
• Consequence: PDE8B NM_001349753.2 5_prime_UTR_premature_start_codon_gain
• Clinical Significance: Benign criteria provided, multiple submitters, no conflicts B:3
• Conservation: PhyloP100: -0.365
• Publications: 0 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 -18 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.26).
• BP6: Variant 5-77210988-C-T is Benign according to our data. Variant chr5-77210988-C-T is described in ClinVar as Benign. ClinVar VariationId is 354145.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars.
• BS1: Variant frequency is greater than expected in population afr. GnomAdExome4 allele frequency = 0.000391 (543/1390084) while in subpopulation AFR AF = 0.0164 (475/28908). AF 95% confidence interval is 0.0152. There are 2 homozygotes in GnomAdExome4. There are 234 alleles in the male GnomAdExome4 subpopulation. Median coverage is 32. This position passed quality control check.
• BS2: High AC in GnomAd4 at 606 AD,Unknown gene.

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_001349753.2. You can select a different transcript below to see updated ACMG assignments.

RefSeq Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	PDE8B	NM_003719.5	MANE Select	c.63C>T	p.Asp21Asp	synonymous	Exon 1 of 22	NP_003710.1	O95263-1
	PDE8B	NM_001349753.2		c.-307C>T		5_prime_UTR_premature_start_codon_gain	Exon 2 of 23	NP_001336682.1	A0A2R8Y4E6
	PDE8B	NM_001349749.3		c.63C>T	p.Asp21Asp	synonymous	Exon 1 of 23	NP_001336678.1

Ensembl Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	PDE8B	ENST00000264917.10	TSL:1 MANE Select	c.63C>T	p.Asp21Asp	synonymous	Exon 1 of 22	ENSP00000264917.6	O95263-1
	PDE8B	ENST00000342343.8	TSL:1	c.63C>T	p.Asp21Asp	synonymous	Exon 1 of 21	ENSP00000345646.4	O95263-4
	PDE8B	ENST00000340978.7	TSL:1	c.63C>T	p.Asp21Asp	synonymous	Exon 1 of 21	ENSP00000345446.3	O95263-6

Frequencies

GnomAD3 genomes AF: 0.00398 AC: 604 AN: 151594 Hom.: 8 Cov.: 32

Gnomad AFR AF: 0.0138

Gnomad AMI AF: 0.00

Gnomad AMR AF: 0.00158

Gnomad ASJ AF: 0.00

Gnomad EAS AF: 0.00

Gnomad SAS AF: 0.00

Gnomad FIN AF: 0.00

Gnomad MID AF: 0.00

Gnomad NFE AF: 0.0000295

Gnomad OTH AF: 0.00336

GnomAD2 exomes AF: 0.000637 AC: 106 AN: 166306 AF XY: 0.000479

Gnomad AFR exome AF: 0.0144

Gnomad AMR exome AF: 0.000257

Gnomad ASJ exome AF: 0.00

Gnomad EAS exome AF: 0.00

Gnomad FIN exome AF: 0.00

Gnomad NFE exome AF: 0.0000131

Gnomad OTH exome AF: 0.000256

GnomAD4 exome AF: 0.000391 AC: 543 AN: 1390084 Hom.: 2 Cov.: 32 AF XY: 0.000339 AC XY: 234 AN XY: 690654

African (AFR) AF: 0.0164 AC: 475 AN: 28908

American (AMR) AF: 0.000468 AC: 18 AN: 38458

Ashkenazi Jewish (ASJ) AF: 0.00 AC: 0 AN: 24196

East Asian (EAS) AF: 0.00 AC: 0 AN: 33064

South Asian (SAS) AF: 0.0000125 AC: 1 AN: 80190

European-Finnish (FIN) AF: 0.00 AC: 0 AN: 35834

Middle Eastern (MID) AF: 0.00 AC: 0 AN: 5430

European-Non Finnish (NFE) AF: 0.0000101 AC: 11 AN: 1086420

Other (OTH) AF: 0.000660 AC: 38 AN: 57584

GnomAD4 genome AF: 0.00399 AC: 606 AN: 151702 Hom.: 8 Cov.: 32 AF XY: 0.00372 AC XY: 276 AN XY: 74164

African (AFR) AF: 0.0138 AC: 573 AN: 41474

American (AMR) AF: 0.00157 AC: 24 AN: 15246

Ashkenazi Jewish (ASJ) AF: 0.00 AC: 0 AN: 3468

East Asian (EAS) AF: 0.00 AC: 0 AN: 5124

South Asian (SAS) AF: 0.00 AC: 0 AN: 4826

European-Finnish (FIN) AF: 0.00 AC: 0 AN: 10438

Middle Eastern (MID) AF: 0.00 AC: 0 AN: 292

European-Non Finnish (NFE) AF: 0.0000295 AC: 2 AN: 67818

Other (OTH) AF: 0.00333 AC: 7 AN: 2104

Alfa AF: 0.000856 Hom.: 0

Bravo AF: 0.00454

ClinVar

ClinVar submissions

Significance: Benign

Revision: criteria provided, multiple submitters, no conflicts

Pathogenic	VUS	Benign	Condition
-	-	2	not provided (2)
-	-	1	Autosomal dominant striatal neurodegeneration type 1 (1)

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.26
CADD	Benign	9.6
DANN	Benign	0.97
PhyloP100		-0.36
PromoterAI		-0.038	Neutral
Mutation Taster		=100/0	polymorphism

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: rs201411330; hg19: chr5-76506813;