8-127396987-T-C

Variant names:

• chr8-127396987-T-C
• rs11985829
• ENST00000501396.6:n.546+23842A>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+23842A>G variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.722 in 152,150 control chromosomes in the GnomAD database, including 39,809 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 0.72 (39809 hom., cov: 32)
• Consequence: CASC8 ENST00000501396.6 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -2.66
• Publications: 5 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=-0.92).
• BA1: GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.768 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
CASC8	NR_117100.1	n.1176+23842A>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+23842A>G		intron_variant	Intron 1 of 2	1
CASC8	ENST00000502082.5	n.1176+23842A>G		intron_variant	Intron 5 of 5	1
CASC8	ENST00000523825.3	n.546+23842A>G		intron_variant	Intron 1 of 1	1

Frequencies

GnomAD3 genomes AF: 0.722 AC: 109715 AN: 152032 Hom.: 39759 Cov.: 32

Gnomad AFR AF: 0.775

Gnomad AMI AF: 0.551

Gnomad AMR AF: 0.733

Gnomad ASJ AF: 0.710

Gnomad EAS AF: 0.713

Gnomad SAS AF: 0.677

Gnomad FIN AF: 0.692

Gnomad MID AF: 0.750

Gnomad NFE AF: 0.697

Gnomad OTH AF: 0.732

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

GnomAD4 genome AF: 0.722 AC: 109821 AN: 152150 Hom.: 39809 Cov.: 32 AF XY: 0.721 AC XY: 53642 AN XY: 74378

African (AFR) AF: 0.776 AC: 32196 AN: 41516

American (AMR) AF: 0.733 AC: 11204 AN: 15280

Ashkenazi Jewish (ASJ) AF: 0.710 AC: 2465 AN: 3472

East Asian (EAS) AF: 0.713 AC: 3694 AN: 5182

South Asian (SAS) AF: 0.677 AC: 3263 AN: 4822

European-Finnish (FIN) AF: 0.692 AC: 7320 AN: 10582

Middle Eastern (MID) AF: 0.759 AC: 223 AN: 294

European-Non Finnish (NFE) AF: 0.697 AC: 47406 AN: 67980

Other (OTH) AF: 0.733 AC: 1549 AN: 2112

Alfa AF: 0.707 Hom.: 20929

Bravo AF: 0.728

Asia WGS AF: 0.700 AC: 2439 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.92
CADD	Benign	0.31
DANN	Benign	0.58
PhyloP100		-2.7

Splicing

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

Other links and lift over

dbSNP: rs11985829; hg19: chr8-128409232;