rs12188950

Variant names:

• chr5-60487490-C-T
• rs12188950
• ENST00000502484.6:c.-90+452G>A

Variant summary

Our verdict is Benign. The variant received -12 ACMG points: 0P and 12B. BP4_Strong BA1

The ENST00000502484.6(PDE4D):​c.-90+452G>A variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.127 in 152,186 control chromosomes in the GnomAD database, including 1,322 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 0.13 (1322 hom., cov: 32)
• Consequence: PDE4D ENST00000502484.6 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 0.132
• Publications: 16 publications found

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]

ENSG00000305967 (HGNC:):

PART1 (HGNC:17263): (prostate androgen-regulated transcript 1) This gene is induced by androgen in prostate adenocarcinoma cells. Multiple alternatively transcript variants have been described for this gene, none of which are predicted to encode a protein product. [provided by RefSeq, Sep 2009]

ACMG classification

Our verdict: Benign. The variant received -12 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.81).
• BA1: GnomAd4 highest subpopulation (NFE) allele frequency at 95% confidence interval = 0.153 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
PDE4D	NM_001165899.2	c.-90+452G>A		intron_variant	Intron 1 of 16		NP_001159371.1
PDE4D	NM_001364599.1	c.-90+8649G>A		intron_variant	Intron 1 of 16		NP_001351528.1
PDE4D	NM_001349241.2	c.-193+452G>A		intron_variant	Intron 1 of 17		NP_001336170.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
PDE4D	ENST00000502484.6	c.-90+452G>A		intron_variant	Intron 1 of 16	1		ENSP00000423094.2
PDE4D	ENST00000509355.5	n.157+452G>A		intron_variant	Intron 1 of 2	1
PDE4D	ENST00000505507.6	c.-213+452G>A		intron_variant	Intron 1 of 3	4		ENSP00000425910.2

Frequencies

GnomAD3 genomes AF: 0.127 AC: 19311 AN: 152068 Hom.: 1321 Cov.: 32

Gnomad AFR AF: 0.111

Gnomad AMI AF: 0.0351

Gnomad AMR AF: 0.0981

Gnomad ASJ AF: 0.120

Gnomad EAS AF: 0.00231

Gnomad SAS AF: 0.0902

Gnomad FIN AF: 0.135

Gnomad MID AF: 0.136

Gnomad NFE AF: 0.156

Gnomad OTH AF: 0.122

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

GnomAD4 genome AF: 0.127 AC: 19317 AN: 152186 Hom.: 1322 Cov.: 32 AF XY: 0.124 AC XY: 9224 AN XY: 74408

African (AFR) AF: 0.111 AC: 4621 AN: 41542

American (AMR) AF: 0.0979 AC: 1498 AN: 15296

Ashkenazi Jewish (ASJ) AF: 0.120 AC: 417 AN: 3470

East Asian (EAS) AF: 0.00212 AC: 11 AN: 5190

South Asian (SAS) AF: 0.0901 AC: 434 AN: 4818

European-Finnish (FIN) AF: 0.135 AC: 1427 AN: 10580

Middle Eastern (MID) AF: 0.143 AC: 42 AN: 294

European-Non Finnish (NFE) AF: 0.156 AC: 10580 AN: 67972

Other (OTH) AF: 0.121 AC: 255 AN: 2112

Alfa AF: 0.143 Hom.: 4585

Bravo AF: 0.124

Asia WGS AF: 0.0440 AC: 155 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.81
CADD	Benign	3.0
DANN	Benign	0.47
PhyloP100		0.13
Mutation Taster		=100/0	polymorphism (auto)

Splicing

Find out detailed SpliceAI scores and Pangolin per-transcript scores at spliceailookup.broadinstitute.org

Other links and lift over

dbSNP: rs12188950; hg19: chr5-59783317;