rs6888341

Variant names:

• chr5-59842043-T-C
• rs6888341
• NM_001104631.2:c.455+51125A>G

Your query was ambiguous. Multiple possible variants found:

• chr5-59842043-T-C
• chr5-59842043-T-G

Variant summary

Our verdict is Benign. The variant received -12 ACMG points: 0P and 12B. BP4_Strong BA1

The NM_001104631.2(PDE4D):​c.455+51125A>G variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0931 in 152,006 control chromosomes in the GnomAD database, including 2,044 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 0.093 (2044 hom., cov: 32)
• Consequence: PDE4D NM_001104631.2 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -5.51
• Publications: 1 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

LOC107986350 (HGNC:):

ACMG classification

Our verdict: Benign. The variant received -12 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.9).
• BA1: GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.305 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
PDE4D	NM_001104631.2	c.455+51125A>G		intron_variant	Intron 1 of 14	ENST00000340635.11	NP_001098101.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
PDE4D	ENST00000340635.11	c.455+51125A>G		intron_variant	Intron 1 of 14	1	NM_001104631.2	ENSP00000345502.6

Frequencies

GnomAD3 genomes AF: 0.0931 AC: 14137 AN: 151888 Hom.: 2044 Cov.: 32

Gnomad AFR AF: 0.310

Gnomad AMI AF: 0.00

Gnomad AMR AF: 0.0415

Gnomad ASJ AF: 0.0602

Gnomad EAS AF: 0.000194

Gnomad SAS AF: 0.00166

Gnomad FIN AF: 0.00

Gnomad MID AF: 0.0411

Gnomad NFE AF: 0.00503

Gnomad OTH AF: 0.0713

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

GnomAD4 genome AF: 0.0931 AC: 14156 AN: 152006 Hom.: 2044 Cov.: 32 AF XY: 0.0898 AC XY: 6674 AN XY: 74318

African (AFR) AF: 0.309 AC: 12805 AN: 41422

American (AMR) AF: 0.0414 AC: 632 AN: 15256

Ashkenazi Jewish (ASJ) AF: 0.0602 AC: 209 AN: 3472

East Asian (EAS) AF: 0.000195 AC: 1 AN: 5140

South Asian (SAS) AF: 0.00145 AC: 7 AN: 4818

European-Finnish (FIN) AF: 0.00 AC: 0 AN: 10614

Middle Eastern (MID) AF: 0.0408 AC: 12 AN: 294

European-Non Finnish (NFE) AF: 0.00502 AC: 341 AN: 67966

Other (OTH) AF: 0.0705 AC: 149 AN: 2112

Alfa AF: 0.0620 Hom.: 182

Bravo AF: 0.106

Asia WGS AF: 0.0180 AC: 64 AN: 3476

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.90
CADD	Benign	0.0020
DANN	Benign	0.77
PhyloP100		-5.5
Mutation Taster		=100/0	polymorphism (auto)

Splicing

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

Other links and lift over

dbSNP: rs6888341; hg19: chr5-59137869;