rs40512

Variant names:

• chr5-60509640-C-T
• rs40512
• XM_024446110.2:c.-90+12411G>A

Variant summary

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

The ENST00000504876.2(PART1):​n.218-11380C>T variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.659 in 151,942 control chromosomes in the GnomAD database, including 34,464 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 0.66 (34464 hom., cov: 30)
• Consequence: PART1 ENST00000504876.2 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 0.282
• Publications: 11 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]

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]

ACMG classification

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

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.93).
• BA1: GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.857 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

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	PART1	NR_024617.1		n.712-19764C>T		intron	N/A
	PART1	NR_028509.1		n.493-11380C>T		intron	N/A

Ensembl Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	PART1	ENST00000504876.2	TSL:2	n.218-11380C>T		intron	N/A
	PDE4D	ENST00000506510.6	TSL:4	n.70+12411G>A		intron	N/A
	PART1	ENST00000506884.2	TSL:2	n.301-19764C>T		intron	N/A

Frequencies

GnomAD3 genomes AF: 0.659 AC: 100047 AN: 151822 Hom.: 34406 Cov.: 30

Gnomad AFR AF: 0.865

Gnomad AMI AF: 0.500

Gnomad AMR AF: 0.584

Gnomad ASJ AF: 0.587

Gnomad EAS AF: 0.439

Gnomad SAS AF: 0.730

Gnomad FIN AF: 0.536

Gnomad MID AF: 0.685

Gnomad NFE AF: 0.588

Gnomad OTH AF: 0.631

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

GnomAD4 genome AF: 0.659 AC: 100166 AN: 151942 Hom.: 34464 Cov.: 30 AF XY: 0.656 AC XY: 48683 AN XY: 74256

African (AFR) AF: 0.865 AC: 35842 AN: 41454

American (AMR) AF: 0.584 AC: 8915 AN: 15266

Ashkenazi Jewish (ASJ) AF: 0.587 AC: 2034 AN: 3468

East Asian (EAS) AF: 0.438 AC: 2261 AN: 5158

South Asian (SAS) AF: 0.731 AC: 3515 AN: 4808

European-Finnish (FIN) AF: 0.536 AC: 5646 AN: 10538

Middle Eastern (MID) AF: 0.670 AC: 197 AN: 294

European-Non Finnish (NFE) AF: 0.588 AC: 39955 AN: 67932

Other (OTH) AF: 0.637 AC: 1346 AN: 2114

Alfa AF: 0.609 Hom.: 57729

Bravo AF: 0.666

Asia WGS AF: 0.597 AC: 2075 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.93
CADD	Benign	1.5
DANN	Benign	0.66
PhyloP100		0.28

Splicing

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

MaxEntScan Visualizer can be used to analyze the impact of this mutation on the neighboring sequence.

Other links and lift over

dbSNP: rs40512;

hg19: chr5-59805467;