chr5-60498403-G-T

Position:

• chr5-60498403-G-T

Variant summary

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

The XM_024446110.2(PDE4D):​c.-90+23648C>A variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.386 in 152,022 control chromosomes in the GnomAD database, including 11,566 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 0.39 (11566 hom., cov: 32)
• Consequence: PDE4D XM_024446110.2 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 0.980

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:):

ACMG classification

Verdict is Benign. Variant got -12 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.8).
• BA1: GnomAd4 highest subpopulation (SAS) allele frequency at 95% confidence interval = 0.518 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
PDE4D	XM_024446110.2	c.-90+23648C>A		intron_variant			XP_024301878.1
PDE4D	XM_024446112.2	c.-90+23648C>A		intron_variant			XP_024301880.1
PART1	NR_024617.1	n.711+9980G>T		intron_variant
PART1	NR_028509.1	n.492+9980G>T		intron_variant

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
PART1	ENST00000504876.2	n.217+9980G>T		intron_variant		2
PDE4D	ENST00000506510.6	n.70+23648C>A		intron_variant		4
PART1	ENST00000506884.2	n.300+9980G>T		intron_variant		2

Frequencies

GnomAD3 genomes AF: 0.386 AC: 58589 AN: 151904 Hom.: 11547 Cov.: 32

Gnomad AFR AF: 0.311

Gnomad AMI AF: 0.451

Gnomad AMR AF: 0.413

Gnomad ASJ AF: 0.344

Gnomad EAS AF: 0.419

Gnomad SAS AF: 0.535

Gnomad FIN AF: 0.422

Gnomad MID AF: 0.421

Gnomad NFE AF: 0.407

Gnomad OTH AF: 0.388

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

GnomAD4 genome AF: 0.386 AC: 58628 AN: 152022 Hom.: 11566 Cov.: 32 AF XY: 0.390 AC XY: 28979 AN XY: 74306

Gnomad4 AFR AF: 0.310

Gnomad4 AMR AF: 0.413

Gnomad4 ASJ AF: 0.344

Gnomad4 EAS AF: 0.419

Gnomad4 SAS AF: 0.536

Gnomad4 FIN AF: 0.422

Gnomad4 NFE AF: 0.407

Gnomad4 OTH AF: 0.395

Alfa AF: 0.397 Hom.: 2964

Bravo AF: 0.380

Asia WGS AF: 0.479 AC: 1663 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.80
CADD	Benign	8.9
DANN	Benign	0.67

Splicing

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

Publications

LitVar

Other links and lift over

dbSNP: rs27653; hg19: chr5-59794230;