ENST00000504876.2:n.218-2004A>G

Variant names:

• chr5-60519016-A-G
• rs26954
• ENST00000504876.2:n.218-2004A>G

Variant summary

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

The ENST00000504876.2(PART1):​n.218-2004A>G variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.732 in 152,120 control chromosomes in the GnomAD database, including 41,672 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 0.73 (41672 hom., cov: 32)
• Consequence: PART1 ENST00000504876.2 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.581
• 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

ACMG classification

Our verdict: Benign. The variant received -12 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.88).
• BA1: GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.888 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
PART1	NR_024617.1	n.712-10388A>G		intron_variant	Intron 1 of 3
PART1	NR_028509.1	n.493-2004A>G		intron_variant	Intron 1 of 1
PDE4D	XM_024446110.2	c.-90+3035T>C		intron_variant	Intron 1 of 17		XP_024301878.1
PDE4D	XM_024446112.2	c.-90+3035T>C		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.218-2004A>G		intron_variant	Intron 1 of 1	2
PDE4D	ENST00000506510.6	n.70+3035T>C		intron_variant	Intron 1 of 2	4
PART1	ENST00000506884.2	n.301-10388A>G		intron_variant	Intron 1 of 3	2

Frequencies

GnomAD3 genomes AF: 0.731 AC: 111188 AN: 152002 Hom.: 41616 Cov.: 32

Gnomad AFR AF: 0.896

Gnomad AMI AF: 0.654

Gnomad AMR AF: 0.704

Gnomad ASJ AF: 0.761

Gnomad EAS AF: 0.573

Gnomad SAS AF: 0.494

Gnomad FIN AF: 0.696

Gnomad MID AF: 0.706

Gnomad NFE AF: 0.672

Gnomad OTH AF: 0.723

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

GnomAD4 genome AF: 0.732 AC: 111286 AN: 152120 Hom.: 41672 Cov.: 32 AF XY: 0.727 AC XY: 54039 AN XY: 74354

African (AFR) AF: 0.896 AC: 37188 AN: 41504

American (AMR) AF: 0.704 AC: 10756 AN: 15278

Ashkenazi Jewish (ASJ) AF: 0.761 AC: 2641 AN: 3472

East Asian (EAS) AF: 0.573 AC: 2959 AN: 5160

South Asian (SAS) AF: 0.493 AC: 2377 AN: 4824

European-Finnish (FIN) AF: 0.696 AC: 7356 AN: 10566

Middle Eastern (MID) AF: 0.704 AC: 207 AN: 294

European-Non Finnish (NFE) AF: 0.672 AC: 45696 AN: 67998

Other (OTH) AF: 0.715 AC: 1511 AN: 2114

Alfa AF: 0.717 Hom.: 12480

Bravo AF: 0.743

Asia WGS AF: 0.554 AC: 1931 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.88
CADD	Benign	0.29
DANN	Benign	0.29
PhyloP100		-0.58

Splicing

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

Other links and lift over

dbSNP: rs26954; hg19: chr5-59814843;