chr5-60143255-T-A

Variant names:

• chr5-60143255-T-A
• rs1544791
• ENST00000502484.6:c.42+42302A>T

Variant summary

Our verdict is Benign. The variant received -8 ACMG points: 0P and 8B. BP4_Strong BS2

The ENST00000502484.6(PDE4D):​c.42+42302A>T variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.000447 in 152,082 control chromosomes in the GnomAD database, with no homozygous occurrence. 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 0.00045 (0 hom., cov: 33)
• Consequence: PDE4D ENST00000502484.6 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.994
• Publications: 21 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 -8 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.61).
• BS2: High AC in GnomAd4 at 68 AD,Unknown gene.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
PDE4D	NM_001165899.2	c.42+42302A>T		intron_variant	Intron 2 of 16		NP_001159371.1
PDE4D	NM_001364599.1	c.42+42302A>T		intron_variant	Intron 2 of 16		NP_001351528.1
PDE4D	NM_001349241.2	c.-62+42302A>T		intron_variant	Intron 2 of 17		NP_001336170.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
PDE4D	ENST00000502484.6	c.42+42302A>T		intron_variant	Intron 2 of 16	1		ENSP00000423094.2
PDE4D	ENST00000509355.5	n.288+42302A>T		intron_variant	Intron 2 of 2	1
PDE4D	ENST00000509368.6	n.*184+4493A>T		intron_variant	Intron 4 of 4	1		ENSP00000423555.2

Frequencies

GnomAD3 genomes AF: 0.000447 AC: 68 AN: 152082 Hom.: 0 Cov.: 33

Gnomad AFR AF: 0.000121

Gnomad AMI AF: 0.00

Gnomad AMR AF: 0.0000655

Gnomad ASJ AF: 0.00

Gnomad EAS AF: 0.00

Gnomad SAS AF: 0.00

Gnomad FIN AF: 0.00

Gnomad MID AF: 0.00

Gnomad NFE AF: 0.000882

Gnomad OTH AF: 0.000956

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

GnomAD4 genome AF: 0.000447 AC: 68 AN: 152082 Hom.: 0 Cov.: 33 AF XY: 0.000417 AC XY: 31 AN XY: 74276

African (AFR) AF: 0.000121 AC: 5 AN: 41394

American (AMR) AF: 0.0000655 AC: 1 AN: 15262

Ashkenazi Jewish (ASJ) AF: 0.00 AC: 0 AN: 3468

East Asian (EAS) AF: 0.00 AC: 0 AN: 5188

South Asian (SAS) AF: 0.00 AC: 0 AN: 4834

European-Finnish (FIN) AF: 0.00 AC: 0 AN: 10590

Middle Eastern (MID) AF: 0.00 AC: 0 AN: 314

European-Non Finnish (NFE) AF: 0.000882 AC: 60 AN: 68030

Other (OTH) AF: 0.000956 AC: 2 AN: 2092

Alfa AF: 0.00 Hom.: 103639

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.61
CADD	Benign	8.1
DANN	Benign	0.79
PhyloP100		-0.99

Splicing

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

Other links and lift over

dbSNP: rs1544791; hg19: chr5-59439082;