5-60491464-T-C

Variant names:

• chr5-60491464-T-C
• rs153031
• ENST00000515734.2:n.2515T>C

Variant summary

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

The NM_001364599.1(PDE4D):​c.-90+4675A>G variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.441 in 151,956 control chromosomes in the GnomAD database, including 16,169 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 0.44 (16169 hom., cov: 31)
  • Failed GnomAD Quality Control
• Consequence: PDE4D NM_001364599.1 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.343
• Publications: 3 publications found

Genes affected

PART1 (HGNC:17263): (prostate androgen-regulated transcript 1) This gene is induced by androgen in prostate adenocarcinoma cells. Multiple alternatively transcript variants have been described for this gene, none of which are predicted to encode a protein product. [provided by RefSeq, Sep 2009]

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

ENSG00000305967 (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 = 0.628 is higher than 0.05.

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_001364599.1. You can select a different transcript below to see updated ACMG assignments.

RefSeq Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	PDE4D	NM_001364599.1		c.-90+4675A>G		intron	N/A	NP_001351528.1	Q08499-11
	PART1	NR_024617.1		n.711+3041T>C		intron	N/A
	PART1	NR_028509.1		n.492+3041T>C		intron	N/A

Ensembl Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	PART1	ENST00000515734.2	TSL:1	n.2515T>C		non_coding_transcript_exon	Exon 2 of 2
	PART1	ENST00000667192.1		n.2230T>C		non_coding_transcript_exon	Exon 2 of 2
	PART1	ENST00000504876.2	TSL:2	n.217+3041T>C		intron	N/A

Frequencies

GnomAD3 genomes AF: 0.441 AC: 66951 AN: 151838 Hom.: 16116 Cov.: 31

Gnomad AFR AF: 0.634

Gnomad AMI AF: 0.276

Gnomad AMR AF: 0.374

Gnomad ASJ AF: 0.341

Gnomad EAS AF: 0.563

Gnomad SAS AF: 0.594

Gnomad FIN AF: 0.273

Gnomad MID AF: 0.427

Gnomad NFE AF: 0.353

Gnomad OTH AF: 0.407

GnomAD4 exome Data not reliable, filtered out with message: AC0 AC: 0 AN: 0 Hom.: 0 Cov.: 0 AC XY: 0 AN XY: 0

African (AFR) AC: 0 AN: 0

American (AMR) AC: 0 AN: 0

Ashkenazi Jewish (ASJ) AC: 0 AN: 0

East Asian (EAS) AC: 0 AN: 0

South Asian (SAS) AC: 0 AN: 0

European-Finnish (FIN) AC: 0 AN: 0

Middle Eastern (MID) AC: 0 AN: 0

European-Non Finnish (NFE) AC: 0 AN: 0

Other (OTH) AC: 0 AN: 0

GnomAD4 genome AF: 0.441 AC: 67049 AN: 151956 Hom.: 16169 Cov.: 31 AF XY: 0.439 AC XY: 32571 AN XY: 74274

African (AFR) AF: 0.634 AC: 26271 AN: 41410

American (AMR) AF: 0.373 AC: 5702 AN: 15276

Ashkenazi Jewish (ASJ) AF: 0.341 AC: 1182 AN: 3470

East Asian (EAS) AF: 0.563 AC: 2912 AN: 5174

South Asian (SAS) AF: 0.593 AC: 2841 AN: 4792

European-Finnish (FIN) AF: 0.273 AC: 2876 AN: 10548

Middle Eastern (MID) AF: 0.425 AC: 125 AN: 294

European-Non Finnish (NFE) AF: 0.353 AC: 24015 AN: 67972

Other (OTH) AF: 0.414 AC: 874 AN: 2110

Alfa AF: 0.387 Hom.: 2070

Bravo AF: 0.452

Asia WGS AF: 0.600 AC: 2082 AN: 3472

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.90
CADD	Benign	4.9
DANN	Benign	0.75
PhyloP100		-0.34

Splicing

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

Other links and lift over

dbSNP: rs153031; hg19: chr5-59787291;