rs7837328

Variant names:

• chr8-127410882-A-G
• rs7837328
• ENST00000501396.6:n.546+9947T>C

Variant summary

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

The ENST00000501396.6(CASC8):​n.546+9947T>C variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.524 in 145,450 control chromosomes in the GnomAD database, including 21,323 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 0.52 (21323 hom., cov: 23)
• Consequence: CASC8 ENST00000501396.6 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.104
• Publications: 56 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=-0.99).
• BA1: GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.631 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
CASC8	NR_117100.1	n.1176+9947T>C		intron_variant	Intron 5 of 5

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
CASC8	ENST00000501396.6	n.546+9947T>C		intron_variant	Intron 1 of 2	1
CASC8	ENST00000502082.5	n.1176+9947T>C		intron_variant	Intron 5 of 5	1
CASC8	ENST00000523825.3	n.546+9947T>C		intron_variant	Intron 1 of 1	1

Frequencies

GnomAD3 genomes AF: 0.525 AC: 76287 AN: 145366 Hom.: 21324 Cov.: 23

Gnomad AFR AF: 0.339

Gnomad AMI AF: 0.473

Gnomad AMR AF: 0.642

Gnomad ASJ AF: 0.585

Gnomad EAS AF: 0.642

Gnomad SAS AF: 0.604

Gnomad FIN AF: 0.539

Gnomad MID AF: 0.591

Gnomad NFE AF: 0.590

Gnomad OTH AF: 0.568

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

GnomAD4 genome AF: 0.524 AC: 76287 AN: 145450 Hom.: 21323 Cov.: 23 AF XY: 0.527 AC XY: 36948 AN XY: 70150

African (AFR) AF: 0.338 AC: 13422 AN: 39714

American (AMR) AF: 0.642 AC: 9303 AN: 14494

Ashkenazi Jewish (ASJ) AF: 0.585 AC: 2022 AN: 3454

East Asian (EAS) AF: 0.642 AC: 3194 AN: 4976

South Asian (SAS) AF: 0.604 AC: 2779 AN: 4602

European-Finnish (FIN) AF: 0.539 AC: 4277 AN: 7936

Middle Eastern (MID) AF: 0.598 AC: 171 AN: 286

European-Non Finnish (NFE) AF: 0.590 AC: 39538 AN: 67064

Other (OTH) AF: 0.571 AC: 1155 AN: 2024

Alfa AF: 0.574 Hom.: 77833

Bravo AF: 0.529

Asia WGS AF: 0.606 AC: 2104 AN: 3470

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.99
CADD	Benign	1.6
DANN	Benign	0.51
PhyloP100		-0.10

Splicing

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

Other links and lift over

dbSNP: rs7837328; hg19: chr8-128423127;