ENST00000501396.6:n.546+38536C>G

Variant names:

• chr8-127382293-G-C
• rs1949808
• ENST00000501396.6:n.546+38536C>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+38536C>G variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.694 in 151,906 control chromosomes in the GnomAD database, including 36,973 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 0.69 (36973 hom., cov: 30)
• Consequence: CASC8 ENST00000501396.6 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.0380
• Publications: 6 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]

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]

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=-0.93).
• BA1: GnomAd4 highest subpopulation (NFE) allele frequency at 95% confidence interval = 0.739 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
CASC21	NR_117099.1	n.458-10211G>C		intron_variant	Intron 3 of 3
CASC8	NR_117100.1	n.1176+38536C>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+38536C>G		intron_variant	Intron 1 of 2	1
CASC8	ENST00000502082.5	n.1176+38536C>G		intron_variant	Intron 5 of 5	1
PCAT1	ENST00000521586.2	n.290-10211G>C		intron_variant	Intron 1 of 1	1

Frequencies

GnomAD3 genomes AF: 0.694 AC: 105357 AN: 151788 Hom.: 36954 Cov.: 30

Gnomad AFR AF: 0.628

Gnomad AMI AF: 0.704

Gnomad AMR AF: 0.631

Gnomad ASJ AF: 0.824

Gnomad EAS AF: 0.511

Gnomad SAS AF: 0.687

Gnomad FIN AF: 0.764

Gnomad MID AF: 0.779

Gnomad NFE AF: 0.745

Gnomad OTH AF: 0.703

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

GnomAD4 genome AF: 0.694 AC: 105420 AN: 151906 Hom.: 36973 Cov.: 30 AF XY: 0.693 AC XY: 51492 AN XY: 74250

African (AFR) AF: 0.627 AC: 25966 AN: 41384

American (AMR) AF: 0.631 AC: 9622 AN: 15260

Ashkenazi Jewish (ASJ) AF: 0.824 AC: 2858 AN: 3468

East Asian (EAS) AF: 0.511 AC: 2634 AN: 5158

South Asian (SAS) AF: 0.688 AC: 3305 AN: 4806

European-Finnish (FIN) AF: 0.764 AC: 8063 AN: 10560

Middle Eastern (MID) AF: 0.772 AC: 224 AN: 290

European-Non Finnish (NFE) AF: 0.745 AC: 50618 AN: 67960

Other (OTH) AF: 0.706 AC: 1489 AN: 2110

Alfa AF: 0.597 Hom.: 1356

Bravo AF: 0.680

Asia WGS AF: 0.606 AC: 2106 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.93
CADD	Benign	2.5
DANN	Benign	0.35
PhyloP100		-0.038

Splicing

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

Other links and lift over

dbSNP: rs1949808; hg19: chr8-128394538;