5-59041654-T-G

Position:

• chr5-59041654-T-G

Variant summary

Our verdict is Benign. Variant got -14 ACMG points: 0P and 14B. BP4_Strong BP6_Moderate BA1

The ENST00000340635.11(PDE4D):​c.809-2683A>C variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0689 in 152,226 control chromosomes in the GnomAD database, including 508 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★).

• Frequency: Genomes: 𝑓 0.069 (508 hom., cov: 32)
• Consequence: PDE4D ENST00000340635.11 intron
• Clinical Significance: Benign criteria provided, single submitter B:1
• Conservation: PhyloP100: -0.0990

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]

(HGNC:):

ACMG classification

Verdict is Benign. Variant got -14 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.79).
• BP6: Variant 5-59041654-T-G is Benign according to our data. Variant chr5-59041654-T-G is described in ClinVar as [Benign]. Clinvar id is 225788.Status of the report is criteria_provided_single_submitter, 1 stars.
• BA1: GnomAd4 highest subpopulation (AMR) allele frequency at 95% confidence interval = 0.102 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
PDE4D	NM_001104631.2	c.809-2683A>C		intron_variant		ENST00000340635.11	NP_001098101.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
PDE4D	ENST00000340635.11	c.809-2683A>C		intron_variant		1	NM_001104631.2	ENSP00000345502
	ENST00000500224.2	n.310+1584T>G		intron_variant, non_coding_transcript_variant		3

Frequencies

GnomAD3 genomes AF: 0.0689 AC: 10482 AN: 152108 Hom.: 510 Cov.: 32

Gnomad AFR AF: 0.0188

Gnomad AMI AF: 0.0406

Gnomad AMR AF: 0.107

Gnomad ASJ AF: 0.0764

Gnomad EAS AF: 0.00115

Gnomad SAS AF: 0.0933

Gnomad FIN AF: 0.0507

Gnomad MID AF: 0.0981

Gnomad NFE AF: 0.0969

Gnomad OTH AF: 0.0770

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

GnomAD4 genome AF: 0.0689 AC: 10481 AN: 152226 Hom.: 508 Cov.: 32 AF XY: 0.0682 AC XY: 5078 AN XY: 74422

Gnomad4 AFR AF: 0.0187

Gnomad4 AMR AF: 0.107

Gnomad4 ASJ AF: 0.0764

Gnomad4 EAS AF: 0.00116

Gnomad4 SAS AF: 0.0938

Gnomad4 FIN AF: 0.0507

Gnomad4 NFE AF: 0.0969

Gnomad4 OTH AF: 0.0762

Alfa AF: 0.0834 Hom.: 364

Bravo AF: 0.0698

Asia WGS AF: 0.0420 AC: 148 AN: 3478

ClinVar

Significance: Benign

Submissions summary: Benign:1

Revision: criteria provided, single submitter

Submissions by phenotype

not provided Benign:1

Benign, criteria provided, single submitter

clinical testing

Labcorp Genetics (formerly Invitae), Labcorp

Jan 22, 2024

- -

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.79
CADD	Benign	3.1
DANN	Benign	0.79

Splicing

Name	Calibrated prediction	Score	Prediction
SpliceAI score (max)		0.0		Details are displayed if max score is > 0.2

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

Publications

LitVar

Other links and lift over

dbSNP: rs1353747; hg19: chr5-58337481;