chr5-60206693-A-G

Position:

• chr5-60206693-A-G

Variant summary

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

The ENST00000502484.6(PDE4D):​c.-89-21006T>C variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.564 in 152,108 control chromosomes in the GnomAD database, including 24,690 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 0.56 (24690 hom., cov: 32)
• Consequence: PDE4D ENST00000502484.6 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 0.729

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=-0.84).
• BA1: GnomAd4 highest subpopulation (AMR) allele frequency at 95% confidence interval = 0.589 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
PDE4D	NM_001165899.2	c.-89-21006T>C		intron_variant
PDE4D	NM_001349241.2	c.-192-21006T>C		intron_variant
PDE4D	NM_001349243.2	c.-673-21006T>C		intron_variant

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
PDE4D	ENST00000502484.6	c.-89-21006T>C		intron_variant		1
PDE4D	ENST00000509368.6	c.-89-21006T>C		intron_variant, NMD_transcript_variant		1
PDE4D	ENST00000509355.5	n.158-21006T>C		intron_variant, non_coding_transcript_variant		1

Frequencies

GnomAD3 genomes AF: 0.564 AC: 85709 AN: 151990 Hom.: 24681 Cov.: 32

Gnomad AFR AF: 0.537

Gnomad AMI AF: 0.759

Gnomad AMR AF: 0.599

Gnomad ASJ AF: 0.583

Gnomad EAS AF: 0.183

Gnomad SAS AF: 0.478

Gnomad FIN AF: 0.638

Gnomad MID AF: 0.551

Gnomad NFE AF: 0.593

Gnomad OTH AF: 0.554

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

GnomAD4 genome AF: 0.564 AC: 85744 AN: 152108 Hom.: 24690 Cov.: 32 AF XY: 0.561 AC XY: 41745 AN XY: 74352

Gnomad4 AFR AF: 0.537

Gnomad4 AMR AF: 0.600

Gnomad4 ASJ AF: 0.583

Gnomad4 EAS AF: 0.183

Gnomad4 SAS AF: 0.478

Gnomad4 FIN AF: 0.638

Gnomad4 NFE AF: 0.593

Gnomad4 OTH AF: 0.547

Alfa AF: 0.583 Hom.: 52813

Bravo AF: 0.562

Asia WGS AF: 0.306 AC: 1065 AN: 3474

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.84
CADD	Benign	10
DANN	Benign	0.74

Splicing

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

Publications

LitVar

Other links and lift over

dbSNP: rs966221; hg19: chr5-59502520;