5-60073967-A-G

Variant names:

• chr5-60073967-A-G
• rs1588265
• ENST00000502484.6:c.43-85250T>C

Variant summary

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

The NM_001165899.2(PDE4D):​c.43-85250T>C variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.294 in 151,750 control chromosomes in the GnomAD database, including 7,322 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 0.29 (7322 hom., cov: 31)
• Consequence: PDE4D NM_001165899.2 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -2.23

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=-0.81).
• BA1: GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.725 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
PDE4D	NM_001165899.2	c.43-85250T>C		intron_variant	Intron 2 of 16		NP_001159371.1
PDE4D	NM_001364599.1	c.43-85250T>C		intron_variant	Intron 2 of 16		NP_001351528.1
PDE4D	NM_001349241.2	c.-61-69621T>C		intron_variant	Intron 2 of 17		NP_001336170.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
PDE4D	ENST00000502484.6	c.43-85250T>C		intron_variant	Intron 2 of 16	1		ENSP00000423094.2
PDE4D	ENST00000509355.5	n.289-85250T>C		intron_variant	Intron 2 of 2	1
PDE4D	ENST00000509368.6	n.*184+73781T>C		intron_variant	Intron 4 of 4	1		ENSP00000423555.2

Frequencies

GnomAD3 genomes AF: 0.294 AC: 44631 AN: 151632 Hom.: 7304 Cov.: 31

Gnomad AFR AF: 0.206

Gnomad AMI AF: 0.249

Gnomad AMR AF: 0.301

Gnomad ASJ AF: 0.298

Gnomad EAS AF: 0.744

Gnomad SAS AF: 0.341

Gnomad FIN AF: 0.307

Gnomad MID AF: 0.285

Gnomad NFE AF: 0.307

Gnomad OTH AF: 0.308

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

GnomAD4 genome AF: 0.294 AC: 44664 AN: 151750 Hom.: 7322 Cov.: 31 AF XY: 0.299 AC XY: 22186 AN XY: 74134

Gnomad4 AFR AF: 0.206

Gnomad4 AMR AF: 0.301

Gnomad4 ASJ AF: 0.298

Gnomad4 EAS AF: 0.745

Gnomad4 SAS AF: 0.342

Gnomad4 FIN AF: 0.307

Gnomad4 NFE AF: 0.307

Gnomad4 OTH AF: 0.316

Alfa AF: 0.310 Hom.: 15793

Bravo AF: 0.290

Asia WGS AF: 0.547 AC: 1896 AN: 3476

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.81
CADD	Benign	0.62
DANN	Benign	0.57

Splicing

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

Publications

LitVar

Other links and lift over

dbSNP: rs1588265; hg19: chr5-59369794;