5-60500907-G-A

Variant names:

• chr5-60500907-G-A
• rs456009
• ENST00000504876.2:n.217+12484G>A

Variant summary

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

The ENST00000504876.2(PART1):​n.217+12484G>A variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.383 in 151,574 control chromosomes in the GnomAD database, including 11,311 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 0.38 (11311 hom., cov: 32)
• Consequence: PART1 ENST00000504876.2 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 0.634
• Publications: 10 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

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 = 0.519 is higher than 0.05.

Variant Effect in Transcripts

ACMG analysis was done for transcript: ENST00000504876.2. You can select a different transcript below to see updated ACMG assignments.

RefSeq Transcripts

Selected	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	PART1	NR_024617.1		n.711+12484G>A		intron	N/A
	PART1	NR_028509.1		n.492+12484G>A		intron	N/A

Ensembl Transcripts

Selected	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	PART1	ENST00000504876.2	TSL:2	n.217+12484G>A		intron	N/A
	PDE4D	ENST00000506510.6	TSL:4	n.70+21144C>T		intron	N/A
	PART1	ENST00000506884.2	TSL:2	n.300+12484G>A		intron	N/A

Frequencies

GnomAD3 genomes AF: 0.383 AC: 58011 AN: 151456 Hom.: 11292 Cov.: 32

Gnomad AFR AF: 0.307

Gnomad AMI AF: 0.449

Gnomad AMR AF: 0.410

Gnomad ASJ AF: 0.340

Gnomad EAS AF: 0.416

Gnomad SAS AF: 0.536

Gnomad FIN AF: 0.416

Gnomad MID AF: 0.364

Gnomad NFE AF: 0.406

Gnomad OTH AF: 0.384

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

GnomAD4 genome AF: 0.383 AC: 58050 AN: 151574 Hom.: 11311 Cov.: 32 AF XY: 0.387 AC XY: 28660 AN XY: 74068

African (AFR) AF: 0.307 AC: 12693 AN: 41348

American (AMR) AF: 0.410 AC: 6256 AN: 15244

Ashkenazi Jewish (ASJ) AF: 0.340 AC: 1179 AN: 3464

East Asian (EAS) AF: 0.416 AC: 2142 AN: 5150

South Asian (SAS) AF: 0.537 AC: 2582 AN: 4812

European-Finnish (FIN) AF: 0.416 AC: 4356 AN: 10462

Middle Eastern (MID) AF: 0.364 AC: 107 AN: 294

European-Non Finnish (NFE) AF: 0.406 AC: 27505 AN: 67790

Other (OTH) AF: 0.391 AC: 822 AN: 2102

Alfa AF: 0.366 Hom.: 3341

Bravo AF: 0.379

Asia WGS AF: 0.480 AC: 1664 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.86
CADD	Benign	4.9
DANN	Benign	0.65
PhyloP100		0.63

Splicing

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

Other links and lift over

dbSNP: rs456009; hg19: chr5-59796734;