rs27653

Variant names:

• chr5-60498403-G-T
• rs27653
• XM_024446110.2:c.-90+23648C>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+9980G>T variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.386 in 152,022 control chromosomes in the GnomAD database, including 11,566 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 0.39 (11566 hom., cov: 32)
• Consequence: PART1 ENST00000504876.2 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 0.980
• Publications: 5 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=-0.8).
• BA1: GnomAd4 highest subpopulation (SAS) allele frequency at 95% confidence interval = 0.518 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.711+9980G>T		intron	N/A
	PART1	NR_028509.1		n.492+9980G>T		intron	N/A

Ensembl Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	PART1	ENST00000504876.2	TSL:2	n.217+9980G>T		intron	N/A
	PDE4D	ENST00000506510.6	TSL:4	n.70+23648C>A		intron	N/A
	PART1	ENST00000506884.2	TSL:2	n.300+9980G>T		intron	N/A

Frequencies

GnomAD3 genomes AF: 0.386 AC: 58589 AN: 151904 Hom.: 11547 Cov.: 32

Gnomad AFR AF: 0.311

Gnomad AMI AF: 0.451

Gnomad AMR AF: 0.413

Gnomad ASJ AF: 0.344

Gnomad EAS AF: 0.419

Gnomad SAS AF: 0.535

Gnomad FIN AF: 0.422

Gnomad MID AF: 0.421

Gnomad NFE AF: 0.407

Gnomad OTH AF: 0.388

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

GnomAD4 genome AF: 0.386 AC: 58628 AN: 152022 Hom.: 11566 Cov.: 32 AF XY: 0.390 AC XY: 28979 AN XY: 74306

African (AFR) AF: 0.310 AC: 12873 AN: 41460

American (AMR) AF: 0.413 AC: 6312 AN: 15272

Ashkenazi Jewish (ASJ) AF: 0.344 AC: 1192 AN: 3468

East Asian (EAS) AF: 0.419 AC: 2161 AN: 5158

South Asian (SAS) AF: 0.536 AC: 2578 AN: 4814

European-Finnish (FIN) AF: 0.422 AC: 4460 AN: 10570

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

European-Non Finnish (NFE) AF: 0.407 AC: 27682 AN: 67962

Other (OTH) AF: 0.395 AC: 835 AN: 2114

Alfa AF: 0.398 Hom.: 5015

Bravo AF: 0.380

Asia WGS AF: 0.479 AC: 1663 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.80
CADD	Benign	8.9
DANN	Benign	0.67
PhyloP100		0.98

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: rs27653;

hg19: chr5-59794230;