rs9292197

chr5-59205796-T-C

Variant summary

Our verdict is Benign. Variant got -12 ACMG points: 0P and 12B. BP4_Strong BA1

The NM_001104631.2(PDE4D):c.647+9981A>G variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.307 in 151,796 control chromosomes in the GnomAD database, including 7,324 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 0.31 (7324 hom., cov: 31)
• Consequence: PDE4D NM_001104631.2 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.312

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 -12 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.9).
• BA1: GnomAd4 highest subpopulation (SAS) allele frequency at 95% confidence interval = 0.332 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
PDE4D	NM_001104631.2	c.647+9981A>G		intron_variant		ENST00000340635.11

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
PDE4D	ENST00000340635.11	c.647+9981A>G		intron_variant		1	NM_001104631.2

Frequencies

GnomAD3 genomes AF: 0.307 AC: 46599 AN: 151678 Hom.: 7315 Cov.: 31

Gnomad AFR AF: 0.320

Gnomad AMI AF: 0.350

Gnomad AMR AF: 0.254

Gnomad ASJ AF: 0.325

Gnomad EAS AF: 0.149

Gnomad SAS AF: 0.346

Gnomad FIN AF: 0.347

Gnomad MID AF: 0.312

Gnomad NFE AF: 0.313

Gnomad OTH AF: 0.289

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

GnomAD4 genome AF: 0.307 AC: 46649 AN: 151796 Hom.: 7324 Cov.: 31 AF XY: 0.305 AC XY: 22630 AN XY: 74150

Gnomad4 AFR AF: 0.321

Gnomad4 AMR AF: 0.254

Gnomad4 ASJ AF: 0.325

Gnomad4 EAS AF: 0.149

Gnomad4 SAS AF: 0.345

Gnomad4 FIN AF: 0.347

Gnomad4 NFE AF: 0.313

Gnomad4 OTH AF: 0.286

Alfa AF: 0.306 Hom.: 1112

Bravo AF: 0.298

Asia WGS AF: 0.269 AC: 938 AN: 3476

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.90
Cadd	Benign	0.63
Dann	Benign	0.72

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: rs9292197; hg19: chr5-58501622;