rs3887175

Variant names:

• chr5-60494629-A-T
• rs3887175
• NM_001364599.1:c.-90+1510T>A

Variant summary

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

The NM_001364599.1(PDE4D):​c.-90+1510T>A variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.149 in 152,070 control chromosomes in the GnomAD database, including 1,763 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 0.15 (1763 hom., cov: 32)
• Consequence: PDE4D NM_001364599.1 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.894
• Publications: 1 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]

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]

ENSG00000305967 (HGNC:):

ACMG classification

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

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.91).
• BA1: GnomAd4 highest subpopulation (NFE) allele frequency at 95% confidence interval = 0.182 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
PDE4D	NM_001364599.1	c.-90+1510T>A		intron_variant	Intron 1 of 16		NP_001351528.1
PART1	NR_024617.1	n.711+6206A>T		intron_variant	Intron 1 of 3
PART1	NR_028509.1	n.492+6206A>T		intron_variant	Intron 1 of 1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
PART1	ENST00000504876.2	n.217+6206A>T		intron_variant	Intron 1 of 1	2
PDE4D	ENST00000506510.6	n.70+27422T>A		intron_variant	Intron 1 of 2	4
PART1	ENST00000506884.2	n.300+6206A>T		intron_variant	Intron 1 of 3	2

Frequencies

GnomAD3 genomes AF: 0.149 AC: 22633 AN: 151952 Hom.: 1762 Cov.: 32

Gnomad AFR AF: 0.131

Gnomad AMI AF: 0.0351

Gnomad AMR AF: 0.115

Gnomad ASJ AF: 0.161

Gnomad EAS AF: 0.00270

Gnomad SAS AF: 0.122

Gnomad FIN AF: 0.132

Gnomad MID AF: 0.146

Gnomad NFE AF: 0.184

Gnomad OTH AF: 0.140

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

GnomAD4 genome AF: 0.149 AC: 22647 AN: 152070 Hom.: 1763 Cov.: 32 AF XY: 0.145 AC XY: 10771 AN XY: 74326

African (AFR) AF: 0.131 AC: 5444 AN: 41496

American (AMR) AF: 0.115 AC: 1752 AN: 15290

Ashkenazi Jewish (ASJ) AF: 0.161 AC: 557 AN: 3470

East Asian (EAS) AF: 0.00251 AC: 13 AN: 5170

South Asian (SAS) AF: 0.121 AC: 581 AN: 4790

European-Finnish (FIN) AF: 0.132 AC: 1396 AN: 10578

Middle Eastern (MID) AF: 0.146 AC: 43 AN: 294

European-Non Finnish (NFE) AF: 0.184 AC: 12537 AN: 67958

Other (OTH) AF: 0.138 AC: 292 AN: 2112

Alfa AF: 0.167 Hom.: 290

Bravo AF: 0.146

Asia WGS AF: 0.0610 AC: 214 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.91
CADD	Benign	0.060
DANN	Benign	0.39
PhyloP100		-0.89

Splicing

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

Other links and lift over

dbSNP: rs3887175; hg19: chr5-59790456;