chr5-60143255-T-C

Variant names:

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

Variant summary

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

The ENST00000502484.6(PDE4D):​c.42+42302A>G variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.663 in 152,124 control chromosomes in the GnomAD database, including 34,061 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 0.66 (34061 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 -12 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.66).
• BA1: GnomAd4 highest subpopulation (NFE) allele frequency at 95% confidence interval = 0.688 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
PDE4D	NM_001165899.2	c.42+42302A>G		intron_variant	Intron 2 of 16		NP_001159371.1
PDE4D	NM_001364599.1	c.42+42302A>G		intron_variant	Intron 2 of 16		NP_001351528.1
PDE4D	NM_001349241.2	c.-62+42302A>G		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>G		intron_variant	Intron 2 of 16	1		ENSP00000423094.2
PDE4D	ENST00000509355.5	n.288+42302A>G		intron_variant	Intron 2 of 2	1
PDE4D	ENST00000509368.6	n.*184+4493A>G		intron_variant	Intron 4 of 4	1		ENSP00000423555.2

Frequencies

GnomAD3 genomes AF: 0.663 AC: 100801 AN: 152006 Hom.: 34058 Cov.: 33

Gnomad AFR AF: 0.646

Gnomad AMI AF: 0.751

Gnomad AMR AF: 0.688

Gnomad ASJ AF: 0.699

Gnomad EAS AF: 0.220

Gnomad SAS AF: 0.665

Gnomad FIN AF: 0.700

Gnomad MID AF: 0.697

Gnomad NFE AF: 0.693

Gnomad OTH AF: 0.660

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

GnomAD4 genome AF: 0.663 AC: 100831 AN: 152124 Hom.: 34061 Cov.: 33 AF XY: 0.659 AC XY: 49034 AN XY: 74360

African (AFR) AF: 0.645 AC: 26767 AN: 41488

American (AMR) AF: 0.688 AC: 10506 AN: 15274

Ashkenazi Jewish (ASJ) AF: 0.699 AC: 2423 AN: 3466

East Asian (EAS) AF: 0.220 AC: 1135 AN: 5170

South Asian (SAS) AF: 0.664 AC: 3208 AN: 4828

European-Finnish (FIN) AF: 0.700 AC: 7405 AN: 10576

Middle Eastern (MID) AF: 0.699 AC: 204 AN: 292

European-Non Finnish (NFE) AF: 0.693 AC: 47120 AN: 68006

Other (OTH) AF: 0.653 AC: 1380 AN: 2114

Alfa AF: 0.681 Hom.: 103639

Bravo AF: 0.661

Asia WGS AF: 0.441 AC: 1538 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.66
CADD	Benign	8.6
DANN	Benign	0.78
PhyloP100		-0.99
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: rs1544791; hg19: chr5-59439082;