5-60100815-T-G

Variant names:

• chr5-60100815-T-G
• rs1396476
• ENST00000502484.6:c.42+84742A>C

Variant summary

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

The ENST00000502484.6(PDE4D):​c.42+84742A>C variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.138 in 152,120 control chromosomes in the GnomAD database, including 1,499 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 0.14 (1499 hom., cov: 32)
• Consequence: PDE4D ENST00000502484.6 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 0.134
• Publications: 4 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=-0.86).
• BA1: GnomAd4 highest subpopulation (SAS) allele frequency at 95% confidence interval = 0.209 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
PDE4D	NM_001165899.2	c.42+84742A>C		intron_variant	Intron 2 of 16		NP_001159371.1
PDE4D	NM_001364599.1	c.42+84742A>C		intron_variant	Intron 2 of 16		NP_001351528.1
PDE4D	NM_001349241.2	c.-62+84742A>C		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+84742A>C		intron_variant	Intron 2 of 16	1		ENSP00000423094.2
PDE4D	ENST00000509355.5	n.288+84742A>C		intron_variant	Intron 2 of 2	1
PDE4D	ENST00000509368.6	n.*184+46933A>C		intron_variant	Intron 4 of 4	1		ENSP00000423555.2

Frequencies

GnomAD3 genomes AF: 0.138 AC: 21001 AN: 152002 Hom.: 1499 Cov.: 32

Gnomad AFR AF: 0.113

Gnomad AMI AF: 0.0559

Gnomad AMR AF: 0.117

Gnomad ASJ AF: 0.148

Gnomad EAS AF: 0.0394

Gnomad SAS AF: 0.220

Gnomad FIN AF: 0.153

Gnomad MID AF: 0.218

Gnomad NFE AF: 0.158

Gnomad OTH AF: 0.133

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

GnomAD4 genome AF: 0.138 AC: 20998 AN: 152120 Hom.: 1499 Cov.: 32 AF XY: 0.138 AC XY: 10295 AN XY: 74402

African (AFR) AF: 0.113 AC: 4693 AN: 41530

American (AMR) AF: 0.117 AC: 1784 AN: 15278

Ashkenazi Jewish (ASJ) AF: 0.148 AC: 515 AN: 3470

East Asian (EAS) AF: 0.0395 AC: 205 AN: 5186

South Asian (SAS) AF: 0.220 AC: 1058 AN: 4820

European-Finnish (FIN) AF: 0.153 AC: 1617 AN: 10600

Middle Eastern (MID) AF: 0.224 AC: 66 AN: 294

European-Non Finnish (NFE) AF: 0.158 AC: 10730 AN: 67914

Other (OTH) AF: 0.132 AC: 279 AN: 2116

Alfa AF: 0.112 Hom.: 297

Bravo AF: 0.129

Asia WGS AF: 0.130 AC: 453 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.86
CADD	Benign	0.87
DANN	Benign	0.80
PhyloP100		0.13
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: rs1396476; hg19: chr5-59396642;