rs10491402

Variant names:

• chr5-60189361-A-G
• rs10491402
• ENST00000502484.6:c.-89-3674T>C

Your query was ambiguous. Multiple possible variants found:

• chr5-60189361-A-G
• chr5-60189361-A-T

Variant summary

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

The ENST00000502484.6(PDE4D):​c.-89-3674T>C variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0452 in 152,270 control chromosomes in the GnomAD database, including 414 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 0.045 (414 hom., cov: 32)
• Consequence: PDE4D ENST00000502484.6 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 0.479
• Publications: 0 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 -12 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.8).
• BA1: GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.135 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
PDE4D	NM_001165899.2	c.-89-3674T>C		intron_variant	Intron 1 of 16		NP_001159371.1
PDE4D	NM_001364599.1	c.-89-3674T>C		intron_variant	Intron 1 of 16		NP_001351528.1
PDE4D	NM_001349241.2	c.-192-3674T>C		intron_variant	Intron 1 of 17		NP_001336170.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
PDE4D	ENST00000502484.6	c.-89-3674T>C		intron_variant	Intron 1 of 16	1		ENSP00000423094.2
PDE4D	ENST00000509355.5	n.158-3674T>C		intron_variant	Intron 1 of 2	1
PDE4D	ENST00000509368.6	n.-89-3674T>C		intron_variant	Intron 1 of 4	1		ENSP00000423555.2

Frequencies

GnomAD3 genomes AF: 0.0452 AC: 6870 AN: 152152 Hom.: 411 Cov.: 32

Gnomad AFR AF: 0.138

Gnomad AMI AF: 0.00329

Gnomad AMR AF: 0.0200

Gnomad ASJ AF: 0.0184

Gnomad EAS AF: 0.000192

Gnomad SAS AF: 0.00558

Gnomad FIN AF: 0.00462

Gnomad MID AF: 0.0158

Gnomad NFE AF: 0.00907

Gnomad OTH AF: 0.0363

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

GnomAD4 genome AF: 0.0452 AC: 6885 AN: 152270 Hom.: 414 Cov.: 32 AF XY: 0.0448 AC XY: 3332 AN XY: 74456

African (AFR) AF: 0.138 AC: 5736 AN: 41522

American (AMR) AF: 0.0200 AC: 306 AN: 15300

Ashkenazi Jewish (ASJ) AF: 0.0184 AC: 64 AN: 3472

East Asian (EAS) AF: 0.000193 AC: 1 AN: 5188

South Asian (SAS) AF: 0.00559 AC: 27 AN: 4832

European-Finnish (FIN) AF: 0.00462 AC: 49 AN: 10616

Middle Eastern (MID) AF: 0.0170 AC: 5 AN: 294

European-Non Finnish (NFE) AF: 0.00907 AC: 617 AN: 68020

Other (OTH) AF: 0.0364 AC: 77 AN: 2114

Alfa AF: 0.0136 Hom.: 74

Bravo AF: 0.0506

Asia WGS AF: 0.0120 AC: 44 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.80
CADD	Benign	3.1
DANN	Benign	0.78
PhyloP100		0.48
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: rs10491402; hg19: chr5-59485188;