rs378854

Variant names:

• chr8-127311574-C-T
• rs378854
• ENST00000501396.6:n.686+11441G>A

Variant summary

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

The ENST00000501396.6(CASC8):​n.686+11441G>A variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.309 in 152,188 control chromosomes in the GnomAD database, including 7,716 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 0.31 (7709 hom., cov: 32)
  • Exomes 𝑓: 0.15 (7 hom.)
• Consequence: CASC8 ENST00000501396.6 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 0.953
• Publications: 30 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=-0.92).
• BA1: GnomAd4 highest subpopulation (SAS) allele frequency at 95% confidence interval = 0.461 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
CASC21	NR_117099.1	n.149-10499C>T		intron_variant	Intron 1 of 3
CASC8	NR_117100.1	n.1177-21514G>A		intron_variant	Intron 5 of 5

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
CASC8	ENST00000501396.6	n.686+11441G>A		intron_variant	Intron 2 of 2	1
CASC8	ENST00000502082.5	n.1177-21514G>A		intron_variant	Intron 5 of 5	1
CASC8	ENST00000523825.3	n.547-21514G>A		intron_variant	Intron 1 of 1	1

Frequencies

GnomAD3 genomes AF: 0.310 AC: 47031 AN: 151806 Hom.: 7704 Cov.: 32

Gnomad AFR AF: 0.201

Gnomad AMI AF: 0.601

Gnomad AMR AF: 0.319

Gnomad ASJ AF: 0.342

Gnomad EAS AF: 0.367

Gnomad SAS AF: 0.478

Gnomad FIN AF: 0.293

Gnomad MID AF: 0.326

Gnomad NFE AF: 0.354

Gnomad OTH AF: 0.325

GnomAD4 exome AF: 0.148 AC: 39 AN: 264 Hom.: 7 Cov.: 0 AF XY: 0.170 AC XY: 30 AN XY: 176

African (AFR) AC: 0 AN: 0

American (AMR) AC: 0 AN: 0

Ashkenazi Jewish (ASJ) AF: 0.0625 AC: 1 AN: 16

East Asian (EAS) AF: 0.00 AC: 0 AN: 4

South Asian (SAS) AF: 0.500 AC: 1 AN: 2

European-Finnish (FIN) AF: 0.0758 AC: 5 AN: 66

Middle Eastern (MID) AF: 0.167 AC: 1 AN: 6

European-Non Finnish (NFE) AF: 0.185 AC: 30 AN: 162

Other (OTH) AF: 0.125 AC: 1 AN: 8

GnomAD4 genome AF: 0.310 AC: 47061 AN: 151924 Hom.: 7709 Cov.: 32 AF XY: 0.310 AC XY: 23052 AN XY: 74280

African (AFR) AF: 0.201 AC: 8308 AN: 41390

American (AMR) AF: 0.319 AC: 4873 AN: 15276

Ashkenazi Jewish (ASJ) AF: 0.342 AC: 1185 AN: 3466

East Asian (EAS) AF: 0.367 AC: 1895 AN: 5170

South Asian (SAS) AF: 0.477 AC: 2294 AN: 4810

European-Finnish (FIN) AF: 0.293 AC: 3085 AN: 10542

Middle Eastern (MID) AF: 0.330 AC: 97 AN: 294

European-Non Finnish (NFE) AF: 0.354 AC: 24083 AN: 67956

Other (OTH) AF: 0.329 AC: 694 AN: 2110

Alfa AF: 0.347 Hom.: 4091

Bravo AF: 0.306

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.92
CADD	Benign	6.0
DANN	Benign	0.51
PhyloP100		0.95

Splicing

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

Other links and lift over

dbSNP: rs378854; hg19: chr8-128323819;