5-58999187-A-G

Variant names:

• chr5-58999187-A-G
• rs7714708
• NM_001104631.2:c.922-5722T>C

Variant summary

Our verdict is Benign. The variant received -14 ACMG points: 0P and 14B. BP4_Strong BP6_Moderate BA1

The NM_001104631.2(PDE4D):​c.922-5722T>C variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.615 in 151,960 control chromosomes in the GnomAD database, including 29,160 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★).

• Frequency: Genomes: 𝑓 0.61 (29160 hom., cov: 32)
• Consequence: PDE4D NM_001104631.2 intron
• Clinical Significance: Benign criteria provided, single submitter B:1
• Conservation: PhyloP100: 0.343
• Publications: 4 publications found

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]

PDE4D Gene-Disease associations (from GenCC):

• acrodysostosis 2 with or without hormone resistance

  Inheritance: AD Classification: DEFINITIVE, STRONG, MODERATE Submitted by: Labcorp Genetics (formerly Invitae), Ambry Genetics, G2P
• acrodysostosis

  Inheritance: AD Classification: SUPPORTIVE Submitted by: Orphanet
• acrodysostosis with multiple hormone resistance

  Inheritance: AD Classification: SUPPORTIVE Submitted by: Orphanet
• chromosome 5q12 deletion syndrome

  Inheritance: Unknown Classification: SUPPORTIVE Submitted by: Orphanet

ACMG classification

Our verdict: Benign. The variant received -14 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.84).
• BP6: Variant 5-58999187-A-G is Benign according to our data. Variant chr5-58999187-A-G is described in ClinVar as [Benign]. Clinvar id is 1275338.Status of the report is criteria_provided_single_submitter, 1 stars.
• BA1: GnomAd4 highest subpopulation (AMR) allele frequency at 95% confidence interval = 0.687 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
PDE4D	NM_001104631.2	c.922-5722T>C		intron_variant	Intron 6 of 14	ENST00000340635.11	NP_001098101.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
PDE4D	ENST00000340635.11	c.922-5722T>C		intron_variant	Intron 6 of 14	1	NM_001104631.2	ENSP00000345502.6

Frequencies

GnomAD3 genomes AF: 0.615 AC: 93373 AN: 151844 Hom.: 29138 Cov.: 32

Gnomad AFR AF: 0.588

Gnomad AMI AF: 0.731

Gnomad AMR AF: 0.698

Gnomad ASJ AF: 0.630

Gnomad EAS AF: 0.298

Gnomad SAS AF: 0.576

Gnomad FIN AF: 0.539

Gnomad MID AF: 0.652

Gnomad NFE AF: 0.649

Gnomad OTH AF: 0.621

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

GnomAD4 genome AF: 0.615 AC: 93437 AN: 151960 Hom.: 29160 Cov.: 32 AF XY: 0.610 AC XY: 45302 AN XY: 74250

African (AFR) AF: 0.587 AC: 24322 AN: 41430

American (AMR) AF: 0.699 AC: 10677 AN: 15284

Ashkenazi Jewish (ASJ) AF: 0.630 AC: 2186 AN: 3470

East Asian (EAS) AF: 0.298 AC: 1539 AN: 5166

South Asian (SAS) AF: 0.577 AC: 2776 AN: 4812

European-Finnish (FIN) AF: 0.539 AC: 5675 AN: 10534

Middle Eastern (MID) AF: 0.650 AC: 191 AN: 294

European-Non Finnish (NFE) AF: 0.649 AC: 44088 AN: 67944

Other (OTH) AF: 0.623 AC: 1318 AN: 2116

Alfa AF: 0.640 Hom.: 97396

Bravo AF: 0.627

Asia WGS AF: 0.451 AC: 1568 AN: 3470

ClinVar

Significance: Benign

Submissions summary: Benign:1

Revision: criteria provided, single submitter

Submissions by phenotype

not provided Benign:1

Jul 09, 2018

GeneDx

Significance: Benign

Review Status: criteria provided, single submitter

Collection Method: clinical testing

- -

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.84
CADD	Benign	5.4
DANN	Benign	0.51
PhyloP100		0.34
Mutation Taster		=100/0	polymorphism (auto)

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

Other links and lift over

dbSNP: rs7714708; hg19: chr5-58295014;