5-60491989-G-T

Variant names:

• chr5-60491989-G-T
• rs152312
• NM_001364599.1:c.-90+4150C>A

Variant summary

Our verdict is Benign. Variant got -8 ACMG points: 0P and 8B. BP4_Strong BS2

The NM_001364599.1(PDE4D):​c.-90+4150C>A variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00436 in 152,150 control chromosomes in the GnomAD database, including 6 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 0.0044 (6 hom., cov: 32)
• Consequence: PDE4D NM_001364599.1 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.496

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]

ACMG classification

Verdict is Benign. Variant got -8 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.85).
• BS2: High AC in GnomAd4 at 663 AD gene.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
PDE4D	NM_001364599.1	c.-90+4150C>A		intron_variant	Intron 1 of 16		NP_001351528.1
PDE4D	XM_024446110.2	c.-90+30062C>A		intron_variant	Intron 1 of 17		XP_024301878.1
PDE4D	XM_024446112.2	c.-90+30062C>A		intron_variant	Intron 1 of 16		XP_024301880.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
PART1	ENST00000667192.1	n.2755G>T		non_coding_transcript_exon_variant	Exon 2 of 2
PART1	ENST00000504876.2	n.217+3566G>T		intron_variant	Intron 1 of 1	2
PDE4D	ENST00000506510.6	n.70+30062C>A		intron_variant	Intron 1 of 2	4

Frequencies

GnomAD3 genomes AF: 0.00436 AC: 663 AN: 152032 Hom.: 6 Cov.: 32

Gnomad AFR AF: 0.0153

Gnomad AMI AF: 0.00

Gnomad AMR AF: 0.00124

Gnomad ASJ AF: 0.00

Gnomad EAS AF: 0.00

Gnomad SAS AF: 0.00

Gnomad FIN AF: 0.00

Gnomad MID AF: 0.00

Gnomad NFE AF: 0.0000441

Gnomad OTH AF: 0.00336

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

GnomAD4 genome AF: 0.00436 AC: 663 AN: 152150 Hom.: 6 Cov.: 32 AF XY: 0.00415 AC XY: 309 AN XY: 74388

Gnomad4 AFR AF: 0.0153

Gnomad4 AMR AF: 0.00124

Gnomad4 ASJ AF: 0.00

Gnomad4 EAS AF: 0.00

Gnomad4 SAS AF: 0.00

Gnomad4 FIN AF: 0.00

Gnomad4 NFE AF: 0.0000441

Gnomad4 OTH AF: 0.00332

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.85
CADD	Benign	1.2
DANN	Benign	0.40

Splicing

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

Publications

LitVar

Other links and lift over

dbSNP: rs152312; hg19: chr5-59787816;