8-127303337-A-G

Variant names:

• chr8-127303337-A-G
• rs283704
• ENST00000501396.6:n.687-13277T>C

Variant summary

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

The ENST00000501396.6(CASC8):​n.687-13277T>C variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.521 in 152,092 control chromosomes in the GnomAD database, including 22,138 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 0.52 (22138 hom., cov: 32)
• Consequence: CASC8 ENST00000501396.6 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.166

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 (EAS) allele frequency at 95% confidence interval = 0.764 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
CASC21	NR_117099.1	n.149-18736A>G		intron_variant	Intron 1 of 3
CASC8	NR_117100.1	n.1177-13277T>C		intron_variant	Intron 5 of 5

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
CASC8	ENST00000501396.6	n.687-13277T>C		intron_variant	Intron 2 of 2	1
CASC8	ENST00000502082.5	n.1177-13277T>C		intron_variant	Intron 5 of 5	1
CASC8	ENST00000523825.3	n.547-13277T>C		intron_variant	Intron 1 of 1	1

Frequencies

GnomAD3 genomes AF: 0.521 AC: 79236 AN: 151974 Hom.: 22122 Cov.: 32

Gnomad AFR AF: 0.309

Gnomad AMI AF: 0.730

Gnomad AMR AF: 0.657

Gnomad ASJ AF: 0.480

Gnomad EAS AF: 0.784

Gnomad SAS AF: 0.707

Gnomad FIN AF: 0.597

Gnomad MID AF: 0.478

Gnomad NFE AF: 0.574

Gnomad OTH AF: 0.542

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

GnomAD4 genome AF: 0.521 AC: 79280 AN: 152092 Hom.: 22138 Cov.: 32 AF XY: 0.531 AC XY: 39470 AN XY: 74346

African (AFR) AF: 0.308 AC: 12793 AN: 41486

American (AMR) AF: 0.657 AC: 10046 AN: 15286

Ashkenazi Jewish (ASJ) AF: 0.480 AC: 1668 AN: 3472

East Asian (EAS) AF: 0.784 AC: 4063 AN: 5180

South Asian (SAS) AF: 0.706 AC: 3401 AN: 4818

European-Finnish (FIN) AF: 0.597 AC: 6304 AN: 10562

Middle Eastern (MID) AF: 0.493 AC: 145 AN: 294

European-Non Finnish (NFE) AF: 0.574 AC: 39043 AN: 67970

Other (OTH) AF: 0.545 AC: 1151 AN: 2112

Alfa AF: 0.563 Hom.: 15849

Bravo AF: 0.515

Asia WGS AF: 0.737 AC: 2561 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.84
CADD	Benign	0.18
DANN	Benign	0.39
PhyloP100		-0.17

Splicing

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

Publications

LitVar

Other links and lift over

dbSNP: rs283704; hg19: chr8-128315582;