8-127414148-G-T

Variant names:

• chr8-127414148-G-T
• rs871135
• ENST00000501396.6:n.546+6681C>A

Variant summary

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

The ENST00000501396.6(CASC8):​n.546+6681C>A variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.532 in 151,974 control chromosomes in the GnomAD database, including 22,568 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 0.53 (22568 hom., cov: 32)
• Consequence: CASC8 ENST00000501396.6 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -1.15
• Publications: 13 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=-0.91).
• BA1: GnomAd4 highest subpopulation (AMR) allele frequency at 95% confidence interval = 0.637 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
POU5F1B	NM_001395745.1	c.-1299G>T		5_prime_UTR_variant	Exon 1 of 2		NP_001382674.1
CASC8	NR_117100.1	n.1176+6681C>A		intron_variant	Intron 5 of 5

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
CASC8	ENST00000501396.6	n.546+6681C>A		intron_variant	Intron 1 of 2	1
CASC8	ENST00000502082.5	n.1176+6681C>A		intron_variant	Intron 5 of 5	1
CASC8	ENST00000523825.3	n.546+6681C>A		intron_variant	Intron 1 of 1	1

Frequencies

GnomAD3 genomes AF: 0.532 AC: 80764 AN: 151856 Hom.: 22567 Cov.: 32

Gnomad AFR AF: 0.350

Gnomad AMI AF: 0.475

Gnomad AMR AF: 0.648

Gnomad ASJ AF: 0.587

Gnomad EAS AF: 0.646

Gnomad SAS AF: 0.611

Gnomad FIN AF: 0.575

Gnomad MID AF: 0.598

Gnomad NFE AF: 0.592

Gnomad OTH AF: 0.576

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

GnomAD4 genome AF: 0.532 AC: 80782 AN: 151974 Hom.: 22568 Cov.: 32 AF XY: 0.536 AC XY: 39821 AN XY: 74278

African (AFR) AF: 0.349 AC: 14479 AN: 41440

American (AMR) AF: 0.648 AC: 9904 AN: 15280

Ashkenazi Jewish (ASJ) AF: 0.587 AC: 2034 AN: 3468

East Asian (EAS) AF: 0.646 AC: 3339 AN: 5170

South Asian (SAS) AF: 0.611 AC: 2945 AN: 4820

European-Finnish (FIN) AF: 0.575 AC: 6059 AN: 10540

Middle Eastern (MID) AF: 0.602 AC: 177 AN: 294

European-Non Finnish (NFE) AF: 0.592 AC: 40191 AN: 67942

Other (OTH) AF: 0.579 AC: 1222 AN: 2110

Alfa AF: 0.557 Hom.: 11597

Bravo AF: 0.529

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.91
CADD	Benign	0.15
DANN	Benign	0.71
PhyloP100		-1.2

Splicing

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

Other links and lift over

dbSNP: rs871135; hg19: chr8-128426393;