ENST00000501396.6:n.687-7660T>C

Variant names:

• chr8-127297720-A-G
• rs283720
• ENST00000501396.6:n.687-7660T>C

Variant summary

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

The ENST00000501396.6(CASC8):​n.687-7660T>C variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.617 in 152,130 control chromosomes in the GnomAD database, including 30,393 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 0.62 (30393 hom., cov: 33)
• Consequence: CASC8 ENST00000501396.6 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.600
• Publications: 8 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=-0.84).
• BA1: GnomAd4 highest subpopulation (NFE) allele frequency at 95% confidence interval = 0.72 is higher than 0.05.

Variant Effect in Transcripts

ACMG analysis was done for transcript: ENST00000501396.6. You can select a different transcript below to see updated ACMG assignments.

RefSeq Transcripts

Selected	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	CASC21	NR_117099.1		n.149-24353A>G		intron	N/A
	CASC8	NR_117100.1		n.1177-7660T>C		intron	N/A

Ensembl Transcripts

Selected	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	CASC8	ENST00000501396.6	TSL:1	n.687-7660T>C		intron	N/A
	CASC8	ENST00000502082.5	TSL:1	n.1177-7660T>C		intron	N/A
	CASC8	ENST00000523825.3	TSL:1	n.547-7660T>C		intron	N/A

Frequencies

GnomAD3 genomes AF: 0.617 AC: 93861 AN: 152012 Hom.: 30384 Cov.: 33

Gnomad AFR AF: 0.432

Gnomad AMI AF: 0.757

Gnomad AMR AF: 0.665

Gnomad ASJ AF: 0.744

Gnomad EAS AF: 0.390

Gnomad SAS AF: 0.588

Gnomad FIN AF: 0.645

Gnomad MID AF: 0.671

Gnomad NFE AF: 0.726

Gnomad OTH AF: 0.636

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

GnomAD4 genome AF: 0.617 AC: 93902 AN: 152130 Hom.: 30393 Cov.: 33 AF XY: 0.611 AC XY: 45427 AN XY: 74370

African (AFR) AF: 0.432 AC: 17912 AN: 41488

American (AMR) AF: 0.665 AC: 10157 AN: 15280

Ashkenazi Jewish (ASJ) AF: 0.744 AC: 2581 AN: 3470

East Asian (EAS) AF: 0.390 AC: 2022 AN: 5178

South Asian (SAS) AF: 0.590 AC: 2849 AN: 4830

European-Finnish (FIN) AF: 0.645 AC: 6818 AN: 10572

Middle Eastern (MID) AF: 0.660 AC: 194 AN: 294

European-Non Finnish (NFE) AF: 0.726 AC: 49344 AN: 67992

Other (OTH) AF: 0.632 AC: 1335 AN: 2114

Alfa AF: 0.699 Hom.: 74954

Bravo AF: 0.612

Asia WGS AF: 0.469 AC: 1632 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.84
CADD	Benign	0.77
DANN	Benign	0.63
PhyloP100		-0.60

Splicing

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

Other links and lift over

dbSNP: rs283720; hg19: chr8-128309965;