rs172362

Positions:

• chr5-59561083-A-C
• chr5-59561083-A-G
• chr5-59561083-A-T

Variant summary

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

The NM_001104631.2(PDE4D):​c.455+332085T>G variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.132 in 152,192 control chromosomes in the GnomAD database, including 1,601 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 0.13 (1601 hom., cov: 32)
• Consequence: PDE4D NM_001104631.2 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 0.246

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]

LOC107986347 (HGNC:):

ACMG classification

Verdict is Benign. Variant got -12 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.85).
• BA1: GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.271 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
PDE4D	NM_001104631.2	c.455+332085T>G		intron_variant		ENST00000340635.11	NP_001098101.1
LOC107986347	XR_001742409.2	n.12718T>G		non_coding_transcript_exon_variant	1/2

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
PDE4D	ENST00000340635.11	c.455+332085T>G		intron_variant		1	NM_001104631.2	ENSP00000345502

Frequencies

GnomAD3 genomes AF: 0.132 AC: 20080 AN: 152074 Hom.: 1595 Cov.: 32

Gnomad AFR AF: 0.0491

Gnomad AMI AF: 0.160

Gnomad AMR AF: 0.161

Gnomad ASJ AF: 0.209

Gnomad EAS AF: 0.284

Gnomad SAS AF: 0.167

Gnomad FIN AF: 0.168

Gnomad MID AF: 0.152

Gnomad NFE AF: 0.152

Gnomad OTH AF: 0.132

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

GnomAD4 genome AF: 0.132 AC: 20082 AN: 152192 Hom.: 1601 Cov.: 32 AF XY: 0.134 AC XY: 9954 AN XY: 74388

Gnomad4 AFR AF: 0.0490

Gnomad4 AMR AF: 0.160

Gnomad4 ASJ AF: 0.209

Gnomad4 EAS AF: 0.283

Gnomad4 SAS AF: 0.166

Gnomad4 FIN AF: 0.168

Gnomad4 NFE AF: 0.152

Gnomad4 OTH AF: 0.141

Alfa AF: 0.127 Hom.: 824

Bravo AF: 0.130

Asia WGS AF: 0.291 AC: 1010 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.85
CADD	Benign	2.7
DANN	Benign	0.67

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: rs172362; hg19: chr5-58856909;