5-60143255-T-C

Position:

• chr5-60143255-T-C

Variant summary

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

The ENST00000502484.6(PDE4D):​c.42+42302A>G variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.663 in 152,124 control chromosomes in the GnomAD database, including 34,061 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 0.66 (34061 hom., cov: 33)
• Consequence: PDE4D ENST00000502484.6 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.994

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=-0.66).
• BA1: GnomAd4 highest subpopulation (NFE) allele frequency at 95% confidence interval = 0.688 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
PDE4D	NM_001165899.2	c.42+42302A>G		intron_variant			NP_001159371.1
PDE4D	NM_001349241.2	c.-62+42302A>G		intron_variant			NP_001336170.1
PDE4D	NM_001349243.2	c.-543+42302A>G		intron_variant			NP_001336172.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
PDE4D	ENST00000502484.6	c.42+42302A>G		intron_variant		1		ENSP00000423094
PDE4D	ENST00000509368.6	c.*184+4493A>G		intron_variant, NMD_transcript_variant		1		ENSP00000423555
PDE4D	ENST00000509355.5	n.288+42302A>G		intron_variant, non_coding_transcript_variant		1

Frequencies

GnomAD3 genomes AF: 0.663 AC: 100801 AN: 152006 Hom.: 34058 Cov.: 33

Gnomad AFR AF: 0.646

Gnomad AMI AF: 0.751

Gnomad AMR AF: 0.688

Gnomad ASJ AF: 0.699

Gnomad EAS AF: 0.220

Gnomad SAS AF: 0.665

Gnomad FIN AF: 0.700

Gnomad MID AF: 0.697

Gnomad NFE AF: 0.693

Gnomad OTH AF: 0.660

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

GnomAD4 genome AF: 0.663 AC: 100831 AN: 152124 Hom.: 34061 Cov.: 33 AF XY: 0.659 AC XY: 49034 AN XY: 74360

Gnomad4 AFR AF: 0.645

Gnomad4 AMR AF: 0.688

Gnomad4 ASJ AF: 0.699

Gnomad4 EAS AF: 0.220

Gnomad4 SAS AF: 0.664

Gnomad4 FIN AF: 0.700

Gnomad4 NFE AF: 0.693

Gnomad4 OTH AF: 0.653

Alfa AF: 0.682 Hom.: 68989

Bravo AF: 0.661

Asia WGS AF: 0.441 AC: 1538 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.66
CADD	Benign	8.6
DANN	Benign	0.78

Splicing

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

Publications

LitVar

Other links and lift over

dbSNP: rs1544791; hg19: chr5-59439082;