rs143090133

chr5-58989926-G-GA

Variant summary

Our verdict is Benign. Variant got -16 ACMG points: 0P and 16B. BP6_Very_Strong BS1 BS2

The NM_001104631.2(PDE4D):c.1288-8_1288-7insT variant causes a splice region, splice polypyrimidine tract, intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00926 in 1,466,354 control chromosomes in the GnomAD database, including 85 homozygotes. Variant has been reported in ClinVar as Likely benign (★★).

• Frequency:
  • Genomes: 𝑓 0.015 (26 hom., cov: 32)
  • Exomes 𝑓: 0.0086 (59 hom.)
• Consequence: PDE4D NM_001104631.2 splice_region, splice_polypyrimidine_tract, intron
• Clinical Significance: Benign/Likely benign criteria provided, multiple submitters, no conflicts B:4
• Conservation: PhyloP100: 1.08

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 -16 ACMG points.

• BP6: Variant 5-58989926-G-GA is Benign according to our data. Variant chr5-58989926-G-GA is described in ClinVar as [Likely_benign]. Clinvar id is 235668.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars.
• BS1: Variant frequency is greater than expected in population afr. gnomad4 allele frequency = 0.0154 (2323/151302) while in subpopulation AFR AF= 0.0339 (1399/41252). AF 95% confidence interval is 0.0324. There are 26 homozygotes in gnomad4. There are 1067 alleles in male gnomad4 subpopulation. This position pass quality control queck.
• BS2: High AC in GnomAd at 2323 AD gene.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
PDE4D	NM_001104631.2	c.1288-8_1288-7insT		splice_region_variant, splice_polypyrimidine_tract_variant, intron_variant		ENST00000340635.11

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
PDE4D	ENST00000340635.11	c.1288-8_1288-7insT		splice_region_variant, splice_polypyrimidine_tract_variant, intron_variant		1	NM_001104631.2

Frequencies

GnomAD3 genomes AF: 0.0154 AC: 2323 AN: 151184 Hom.: 26 Cov.: 32

Gnomad AFR AF: 0.0340

Gnomad AMI AF: 0.00883

Gnomad AMR AF: 0.00514

Gnomad ASJ AF: 0.00

Gnomad EAS AF: 0.00

Gnomad SAS AF: 0.00126

Gnomad FIN AF: 0.00918

Gnomad MID AF: 0.0127

Gnomad NFE AF: 0.0105

Gnomad OTH AF: 0.0102

GnomAD3 exomes AF: 0.00759 AC: 1563 AN: 206014 Hom.: 13 AF XY: 0.00681 AC XY: 765 AN XY: 112412

Gnomad AFR exome AF: 0.0315

Gnomad AMR exome AF: 0.00437

Gnomad ASJ exome AF: 0.000270

Gnomad EAS exome AF: 0.00

Gnomad SAS exome AF: 0.000874

Gnomad FIN exome AF: 0.00912

Gnomad NFE exome AF: 0.00804

Gnomad OTH exome AF: 0.00593

GnomAD4 exome AF: 0.00855 AC: 11250 AN: 1315052 Hom.: 59 Cov.: 20 AF XY: 0.00824 AC XY: 5431 AN XY: 659012

Gnomad4 AFR exome AF: 0.0297

Gnomad4 AMR exome AF: 0.00463

Gnomad4 ASJ exome AF: 0.000297

Gnomad4 EAS exome AF: 0.00

Gnomad4 SAS exome AF: 0.000981

Gnomad4 FIN exome AF: 0.0100

Gnomad4 NFE exome AF: 0.00916

Gnomad4 OTH exome AF: 0.00820

GnomAD4 genome AF: 0.0154 AC: 2323 AN: 151302 Hom.: 26 Cov.: 32 AF XY: 0.0144 AC XY: 1067 AN XY: 73912

Gnomad4 AFR AF: 0.0339

Gnomad4 AMR AF: 0.00514

Gnomad4 ASJ AF: 0.00

Gnomad4 EAS AF: 0.00

Gnomad4 SAS AF: 0.00126

Gnomad4 FIN AF: 0.00918

Gnomad4 NFE AF: 0.0105

Gnomad4 OTH AF: 0.0101

Alfa AF: 0.0117 Hom.: 2

Bravo AF: 0.0157

Asia WGS AF: 0.00289 AC: 10 AN: 3478

ClinVar

Significance: Benign/Likely benign

Submissions summary: Benign:4

Revision: criteria provided, multiple submitters, no conflicts

Submissions by phenotype

not provided Benign:3

Likely benign, criteria provided, single submitter	clinical testing	GeneDx	Jul 14, 2018	- -
Benign, criteria provided, single submitter	clinical testing	Invitae	Jan 31, 2024	- -
Likely benign, criteria provided, single submitter	clinical testing	Center for Pediatric Genomic Medicine, Children's Mercy Hospital and Clinics	Feb 01, 2016	- -

Acrodysostosis Benign:1

Likely benign, criteria provided, single submitter

clinical testing

Illumina Laboratory Services, Illumina

Jun 14, 2016

- -

Computational scores

Source: dbNSFP v4.3

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: rs143090133; hg19: chr5-58285753;