rs10956361

Variant names:

• chr8-127337861-G-A
• rs10956361
• ENST00000501396.6:n.547-14707C>T

Variant summary

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

The ENST00000501396.6(CASC8):​n.547-14707C>T variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.403 in 151,988 control chromosomes in the GnomAD database, including 12,578 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 0.40 (12578 hom., cov: 33)
• Consequence: CASC8 ENST00000501396.6 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -1.43
• Publications: 11 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]

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=-0.99).
• BA1: GnomAd4 highest subpopulation (AMR) allele frequency at 95% confidence interval = 0.51 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
CASC21	NR_117099.1	n.303-1420G>A		intron_variant	Intron 2 of 3
CASC8	NR_117100.1	n.1177-47801C>T		intron_variant	Intron 5 of 5

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
CASC8	ENST00000501396.6	n.547-14707C>T		intron_variant	Intron 1 of 2	1
CASC8	ENST00000502082.5	n.1177-47801C>T		intron_variant	Intron 5 of 5	1
CASC8	ENST00000523825.3	n.547-47801C>T		intron_variant	Intron 1 of 1	1

Frequencies

GnomAD3 genomes AF: 0.403 AC: 61182 AN: 151870 Hom.: 12557 Cov.: 33

Gnomad AFR AF: 0.365

Gnomad AMI AF: 0.573

Gnomad AMR AF: 0.519

Gnomad ASJ AF: 0.410

Gnomad EAS AF: 0.456

Gnomad SAS AF: 0.492

Gnomad FIN AF: 0.290

Gnomad MID AF: 0.497

Gnomad NFE AF: 0.402

Gnomad OTH AF: 0.448

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

GnomAD4 genome AF: 0.403 AC: 61242 AN: 151988 Hom.: 12578 Cov.: 33 AF XY: 0.403 AC XY: 29952 AN XY: 74280

African (AFR) AF: 0.365 AC: 15127 AN: 41438

American (AMR) AF: 0.519 AC: 7931 AN: 15274

Ashkenazi Jewish (ASJ) AF: 0.410 AC: 1423 AN: 3468

East Asian (EAS) AF: 0.457 AC: 2359 AN: 5166

South Asian (SAS) AF: 0.493 AC: 2375 AN: 4818

European-Finnish (FIN) AF: 0.290 AC: 3054 AN: 10542

Middle Eastern (MID) AF: 0.507 AC: 149 AN: 294

European-Non Finnish (NFE) AF: 0.402 AC: 27356 AN: 67974

Other (OTH) AF: 0.450 AC: 948 AN: 2106

Alfa AF: 0.402 Hom.: 5345

Bravo AF: 0.419

Asia WGS AF: 0.473 AC: 1642 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.99
CADD	Benign	1.4
DANN	Benign	0.63
PhyloP100		-1.4

Splicing

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

Other links and lift over

dbSNP: rs10956361; hg19: chr8-128350106;