8-127402647-T-C

Variant names:

• chr8-127402647-T-C
• rs7013278
• ENST00000501396.6:n.546+18182A>G

Variant summary

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

The ENST00000501396.6(CASC8):​n.546+18182A>G variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.593 in 152,008 control chromosomes in the GnomAD database, including 27,466 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 0.59 (27466 hom., cov: 32)
• Consequence: CASC8 ENST00000501396.6 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.554
• Publications: 23 publications found

Genes affected

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

POU5F1B (HGNC:9223): (POU class 5 homeobox 1B) This intronless gene was thought to be a transcribed pseudogene of POU class 5 homeobox 1, however, it has been reported that this gene can encode a functional protein. The encoded protein is nearly the same length as and highly similar to the POU class 5 homeobox 1 transcription factor, has been shown to be a weak transcriptional activator and may play a role in carcinogenesis and eye development. [provided by RefSeq, Apr 2009]

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]

ACMG classification

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

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.95).
• BA1: GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.688 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
CASC8	NR_117100.1	n.1176+18182A>G		intron_variant	Intron 5 of 5

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
CASC8	ENST00000501396.6	n.546+18182A>G		intron_variant	Intron 1 of 2	1
CASC8	ENST00000502082.5	n.1176+18182A>G		intron_variant	Intron 5 of 5	1
CASC8	ENST00000523825.3	n.546+18182A>G		intron_variant	Intron 1 of 1	1

Frequencies

GnomAD3 genomes AF: 0.593 AC: 90129 AN: 151890 Hom.: 27451 Cov.: 32

Gnomad AFR AF: 0.454

Gnomad AMI AF: 0.512

Gnomad AMR AF: 0.677

Gnomad ASJ AF: 0.637

Gnomad EAS AF: 0.707

Gnomad SAS AF: 0.648

Gnomad FIN AF: 0.661

Gnomad MID AF: 0.636

Gnomad NFE AF: 0.634

Gnomad OTH AF: 0.622

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

GnomAD4 genome AF: 0.593 AC: 90175 AN: 152008 Hom.: 27466 Cov.: 32 AF XY: 0.599 AC XY: 44511 AN XY: 74310

African (AFR) AF: 0.453 AC: 18770 AN: 41412

American (AMR) AF: 0.677 AC: 10346 AN: 15292

Ashkenazi Jewish (ASJ) AF: 0.637 AC: 2211 AN: 3472

East Asian (EAS) AF: 0.707 AC: 3660 AN: 5176

South Asian (SAS) AF: 0.648 AC: 3122 AN: 4818

European-Finnish (FIN) AF: 0.661 AC: 6999 AN: 10582

Middle Eastern (MID) AF: 0.643 AC: 189 AN: 294

European-Non Finnish (NFE) AF: 0.634 AC: 43100 AN: 67952

Other (OTH) AF: 0.625 AC: 1311 AN: 2098

Alfa AF: 0.620 Hom.: 23773

Bravo AF: 0.588

Asia WGS AF: 0.658 AC: 2291 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.95
CADD	Benign	0.75
DANN	Benign	0.57
PhyloP100		-0.55

Splicing

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

Other links and lift over

dbSNP: rs7013278; hg19: chr8-128414892;