ENST00000501396.5:n.546+29560A>C

Variant names:

• chr8-127391269-T-G
• rs7844673
• ENST00000501396.5:n.546+29560A>C

Variant summary

Our verdict is Benign. Variant got -10 ACMG points: 0P and 10B. BP4_Moderate BA1

The ENST00000501396.5(CASC8):​n.546+29560A>C variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0792 in 152,206 control chromosomes in the GnomAD database, including 563 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 0.079 (563 hom., cov: 32)
• Consequence: CASC8 ENST00000501396.5 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 1.89

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

Verdict is Benign. Variant got -10 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.46).
• BA1: GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.111 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
CASC21	NR_117099.1	n.458-1235T>G		intron_variant	Intron 3 of 3
CASC8	NR_117100.1	n.1176+29560A>C		intron_variant	Intron 5 of 5

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
CASC8	ENST00000501396.5	n.546+29560A>C		intron_variant	Intron 1 of 2	1
CASC8	ENST00000502082.5	n.1176+29560A>C		intron_variant	Intron 5 of 5	1
PCAT1	ENST00000521586.2	n.290-1235T>G		intron_variant	Intron 1 of 1	1

Frequencies

GnomAD3 genomes AF: 0.0792 AC: 12041 AN: 152088 Hom.: 560 Cov.: 32

Gnomad AFR AF: 0.114

Gnomad AMI AF: 0.0987

Gnomad AMR AF: 0.0453

Gnomad ASJ AF: 0.0831

Gnomad EAS AF: 0.0695

Gnomad SAS AF: 0.112

Gnomad FIN AF: 0.0892

Gnomad MID AF: 0.108

Gnomad NFE AF: 0.0621

Gnomad OTH AF: 0.0770

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

GnomAD4 genome AF: 0.0792 AC: 12060 AN: 152206 Hom.: 563 Cov.: 32 AF XY: 0.0802 AC XY: 5970 AN XY: 74406

Gnomad4 AFR AF: 0.114

Gnomad4 AMR AF: 0.0452

Gnomad4 ASJ AF: 0.0831

Gnomad4 EAS AF: 0.0696

Gnomad4 SAS AF: 0.112

Gnomad4 FIN AF: 0.0892

Gnomad4 NFE AF: 0.0621

Gnomad4 OTH AF: 0.0781

Alfa AF: 0.0613 Hom.: 472

Bravo AF: 0.0753

Asia WGS AF: 0.0920 AC: 319 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.46
CADD	Benign	20
DANN	Benign	0.82

Splicing

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

Publications

LitVar

Other links and lift over

dbSNP: rs7844673; hg19: chr8-128403514;