rs10036406

chr5-59256487-A-C

Variant summary

Our verdict is Benign. Variant got -10 ACMG points: 0P and 10B. BP4_Moderate BA1

The NM_001104631.2(PDE4D):c.456-40519T>G variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0687 in 152,148 control chromosomes in the GnomAD database, including 463 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 0.069 (463 hom., cov: 32)
• Consequence: PDE4D NM_001104631.2 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 1.33

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 -10 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.35).
• BA1: GnomAd4 highest subpopulation (SAS) allele frequency at 95% confidence interval = 0.0967 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
PDE4D	NM_001104631.2	c.456-40519T>G		intron_variant		ENST00000340635.11

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
PDE4D	ENST00000340635.11	c.456-40519T>G		intron_variant		1	NM_001104631.2

Frequencies

GnomAD3 genomes AF: 0.0688 AC: 10456 AN: 152030 Hom.: 463 Cov.: 32

Gnomad AFR AF: 0.0183

Gnomad AMI AF: 0.104

Gnomad AMR AF: 0.0546

Gnomad ASJ AF: 0.0516

Gnomad EAS AF: 0.0569

Gnomad SAS AF: 0.0992

Gnomad FIN AF: 0.0888

Gnomad MID AF: 0.0854

Gnomad NFE AF: 0.0987

Gnomad OTH AF: 0.0695

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

GnomAD4 genome AF: 0.0687 AC: 10450 AN: 152148 Hom.: 463 Cov.: 32 AF XY: 0.0680 AC XY: 5059 AN XY: 74374

Gnomad4 AFR AF: 0.0182

Gnomad4 AMR AF: 0.0545

Gnomad4 ASJ AF: 0.0516

Gnomad4 EAS AF: 0.0566

Gnomad4 SAS AF: 0.0995

Gnomad4 FIN AF: 0.0888

Gnomad4 NFE AF: 0.0987

Gnomad4 OTH AF: 0.0688

Alfa AF: 0.0833 Hom.: 123

Bravo AF: 0.0642

Asia WGS AF: 0.0780 AC: 271 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.35
Cadd	Benign	16
Dann	Benign	0.84

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: rs10036406; hg19: chr5-58552313;