ENST00000504876.2:n.217+9285C>T

Variant names:

• chr5-60497708-C-T
• rs26955
• ENST00000504876.2:n.217+9285C>T

Variant summary

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

The ENST00000504876.2(PART1):​n.217+9285C>T variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.532 in 152,022 control chromosomes in the GnomAD database, including 22,227 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 0.53 (22227 hom., cov: 32)
• Consequence: PART1 ENST00000504876.2 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 0.00700
• Publications: 4 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=-0.89).
• BA1: GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.67 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
PART1	NR_024617.1	n.711+9285C>T		intron_variant	Intron 1 of 3
PART1	NR_028509.1	n.492+9285C>T		intron_variant	Intron 1 of 1
PDE4D	XM_024446110.2	c.-90+24343G>A		intron_variant	Intron 1 of 17		XP_024301878.1
PDE4D	XM_024446112.2	c.-90+24343G>A		intron_variant	Intron 1 of 16		XP_024301880.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
PART1	ENST00000504876.2	n.217+9285C>T		intron_variant	Intron 1 of 1	2
PDE4D	ENST00000506510.6	n.70+24343G>A		intron_variant	Intron 1 of 2	4
PART1	ENST00000506884.2	n.300+9285C>T		intron_variant	Intron 1 of 3	2

Frequencies

GnomAD3 genomes AF: 0.532 AC: 80746 AN: 151904 Hom.: 22183 Cov.: 32

Gnomad AFR AF: 0.676

Gnomad AMI AF: 0.488

Gnomad AMR AF: 0.490

Gnomad ASJ AF: 0.457

Gnomad EAS AF: 0.424

Gnomad SAS AF: 0.637

Gnomad FIN AF: 0.480

Gnomad MID AF: 0.563

Gnomad NFE AF: 0.466

Gnomad OTH AF: 0.523

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

GnomAD4 genome AF: 0.532 AC: 80849 AN: 152022 Hom.: 22227 Cov.: 32 AF XY: 0.532 AC XY: 39521 AN XY: 74304

African (AFR) AF: 0.676 AC: 28063 AN: 41490

American (AMR) AF: 0.490 AC: 7487 AN: 15268

Ashkenazi Jewish (ASJ) AF: 0.457 AC: 1584 AN: 3468

East Asian (EAS) AF: 0.423 AC: 2183 AN: 5158

South Asian (SAS) AF: 0.638 AC: 3071 AN: 4814

European-Finnish (FIN) AF: 0.480 AC: 5064 AN: 10550

Middle Eastern (MID) AF: 0.558 AC: 164 AN: 294

European-Non Finnish (NFE) AF: 0.466 AC: 31668 AN: 67956

Other (OTH) AF: 0.530 AC: 1120 AN: 2112

Alfa AF: 0.493 Hom.: 24839

Bravo AF: 0.537

Asia WGS AF: 0.554 AC: 1926 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.89
CADD	Benign	3.3
DANN	Benign	0.64
PhyloP100		0.0070

Splicing

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

Other links and lift over

dbSNP: rs26955; hg19: chr5-59793535;