ENST00000501396.6:n.687-4777G>A

Variant names:

• chr8-127294837-C-T
• rs283718
• ENST00000501396.6:n.687-4777G>A

Variant summary

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

The ENST00000501396.6(CASC8):​n.687-4777G>A variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.486 in 152,106 control chromosomes in the GnomAD database, including 19,348 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 0.49 (19348 hom., cov: 32)
• Consequence: CASC8 ENST00000501396.6 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 1.31
• Publications: 7 publications found

Genes affected

CASC8 (HGNC:45129): (cancer susceptibility 8)

PCAT1 (HGNC:43022): (prostate cancer associated transcript 1) This gene produces a long non-coding RNA that promotes cell proliferation and is upregulated in prostate, colorectal, and other cancers. This RNA negatively regulates the BRCA2 tumor suppressor protein and positively regulates Myc oncoprotein. It contains binding sites for microRNAs, and may act as a sponge for microRNAs that regulate cell growth pathways. [provided by RefSeq, Dec 2017]

CASC21 (HGNC:49836): (cancer susceptibility 21)

ACMG classification

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

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.62).
• BA1: GnomAd4 highest subpopulation (NFE) allele frequency at 95% confidence interval = 0.584 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
CASC21	NR_117099.1	n.149-27236C>T		intron_variant	Intron 1 of 3
CASC8	NR_117100.1	n.1177-4777G>A		intron_variant	Intron 5 of 5

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
CASC8	ENST00000501396.6	n.687-4777G>A		intron_variant	Intron 2 of 2	1
CASC8	ENST00000502082.5	n.1177-4777G>A		intron_variant	Intron 5 of 5	1
CASC8	ENST00000523825.3	n.547-4777G>A		intron_variant	Intron 1 of 1	1

Frequencies

GnomAD3 genomes AF: 0.486 AC: 73872 AN: 151988 Hom.: 19340 Cov.: 32

Gnomad AFR AF: 0.287

Gnomad AMI AF: 0.431

Gnomad AMR AF: 0.570

Gnomad ASJ AF: 0.579

Gnomad EAS AF: 0.318

Gnomad SAS AF: 0.459

Gnomad FIN AF: 0.545

Gnomad MID AF: 0.563

Gnomad NFE AF: 0.588

Gnomad OTH AF: 0.524

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

GnomAD4 genome AF: 0.486 AC: 73907 AN: 152106 Hom.: 19348 Cov.: 32 AF XY: 0.482 AC XY: 35824 AN XY: 74358

African (AFR) AF: 0.287 AC: 11887 AN: 41478

American (AMR) AF: 0.570 AC: 8720 AN: 15288

Ashkenazi Jewish (ASJ) AF: 0.579 AC: 2009 AN: 3470

East Asian (EAS) AF: 0.318 AC: 1649 AN: 5178

South Asian (SAS) AF: 0.461 AC: 2218 AN: 4816

European-Finnish (FIN) AF: 0.545 AC: 5761 AN: 10566

Middle Eastern (MID) AF: 0.561 AC: 165 AN: 294

European-Non Finnish (NFE) AF: 0.588 AC: 40011 AN: 68000

Other (OTH) AF: 0.520 AC: 1095 AN: 2106

Alfa AF: 0.556 Hom.: 75937

Bravo AF: 0.480

Asia WGS AF: 0.362 AC: 1260 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.62
CADD	Benign	16
DANN	Benign	0.58
PhyloP100		1.3

Splicing

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

Other links and lift over

dbSNP: rs283718; hg19: chr8-128307082;