rs6450512

Positions:

• chr5-59215675-G-A
• chr5-59215675-G-C

Variant summary

Our verdict is Benign. Variant got -14 ACMG points: 0P and 14B. BP4_Strong BP6_Moderate BA1

The NM_001104631.2(PDE4D):​c.647+102C>T variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.426 in 931,594 control chromosomes in the GnomAD database, including 91,558 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★).

• Frequency:
  • Genomes: 𝑓 0.51 (22124 hom., cov: 31)
  • Exomes 𝑓: 0.41 (69434 hom.)
• Consequence: PDE4D NM_001104631.2 intron
• Clinical Significance: Benign criteria provided, single submitter B:1
• Conservation: PhyloP100: -0.0400

Genes affected

PDE4D (HGNC:8783): (phosphodiesterase 4D) This gene encodes one of four mammalian counterparts to the fruit fly 'dunce' gene. The encoded protein has 3',5'-cyclic-AMP phosphodiesterase activity and degrades cAMP, which acts as a signal transduction molecule in multiple cell types. This gene uses different promoters to generate multiple alternatively spliced transcript variants that encode functional proteins.[provided by RefSeq, Sep 2009]

ACMG classification

Verdict is Benign. Variant got -14 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.91).
• BP6: Variant 5-59215675-G-A is Benign according to our data. Variant chr5-59215675-G-A is described in ClinVar as [Benign]. Clinvar id is 1241786.Status of the report is criteria_provided_single_submitter, 1 stars.
• BA1: GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.783 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
PDE4D	NM_001104631.2	c.647+102C>T		intron_variant		ENST00000340635.11

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
PDE4D	ENST00000340635.11	c.647+102C>T		intron_variant		1	NM_001104631.2

Frequencies

GnomAD3 genomes AF: 0.505 AC: 76621 AN: 151674 Hom.: 22063 Cov.: 31

Gnomad AFR AF: 0.790

Gnomad AMI AF: 0.409

Gnomad AMR AF: 0.442

Gnomad ASJ AF: 0.312

Gnomad EAS AF: 0.565

Gnomad SAS AF: 0.573

Gnomad FIN AF: 0.413

Gnomad MID AF: 0.389

Gnomad NFE AF: 0.364

Gnomad OTH AF: 0.457

GnomAD4 exome AF: 0.410 AC: 319724 AN: 779802 Hom.: 69434 Cov.: 10 AF XY: 0.412 AC XY: 168354 AN XY: 408434

Gnomad4 AFR exome AF: 0.797

Gnomad4 AMR exome AF: 0.436

Gnomad4 ASJ exome AF: 0.296

Gnomad4 EAS exome AF: 0.551

Gnomad4 SAS exome AF: 0.556

Gnomad4 FIN exome AF: 0.405

Gnomad4 NFE exome AF: 0.370

Gnomad4 OTH exome AF: 0.418

GnomAD4 genome AF: 0.506 AC: 76737 AN: 151792 Hom.: 22124 Cov.: 31 AF XY: 0.505 AC XY: 37434 AN XY: 74166

Gnomad4 AFR AF: 0.790

Gnomad4 AMR AF: 0.442

Gnomad4 ASJ AF: 0.312

Gnomad4 EAS AF: 0.564

Gnomad4 SAS AF: 0.572

Gnomad4 FIN AF: 0.413

Gnomad4 NFE AF: 0.364

Gnomad4 OTH AF: 0.462

Alfa AF: 0.384 Hom.: 16511

Bravo AF: 0.519

Asia WGS AF: 0.635 AC: 2208 AN: 3478

ClinVar

Significance: Benign

Submissions summary: Benign:1

Revision: criteria provided, single submitter

Submissions by phenotype

not provided Benign:1

Benign, criteria provided, single submitter

clinical testing

GeneDx

Jul 09, 2018

- -

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.91
CADD	Benign	0.74
DANN	Benign	0.38

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

Publications

LitVar

Other links and lift over

dbSNP: rs6450512; hg19: chr5-58511501; COSMIC: COSV58940168;