rs1668875

chr8-127328858-G-C

Variant summary

Our verdict is Benign. Variant got -12 ACMG points: 0P and 12B. BP4_Strong BA1

The NR_117099.1(CASC21):n.302+6632G>C variant causes a intron, non coding transcript change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.416 in 152,022 control chromosomes in the GnomAD database, including 13,489 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 0.42 (13489 hom., cov: 32)
• Consequence: CASC21 NR_117099.1 intron, non_coding_transcript
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 0.0490

Genes affected

CASC8 (HGNC:45129): (cancer susceptibility 8)

CASC21 (HGNC:):

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

Verdict is Benign. Variant got -12 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.91).
• BA1: GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.543 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
CASC21	NR_117099.1	n.302+6632G>C		intron_variant, non_coding_transcript_variant
CASC8	NR_117100.1	n.1177-38798C>G		intron_variant, non_coding_transcript_variant

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
CASC8	ENST00000502082.5	n.1177-38798C>G		intron_variant, non_coding_transcript_variant		1

Frequencies

GnomAD3 genomes AF: 0.416 AC: 63119 AN: 151904 Hom.: 13462 Cov.: 32

Gnomad AFR AF: 0.383

Gnomad AMI AF: 0.622

Gnomad AMR AF: 0.512

Gnomad ASJ AF: 0.427

Gnomad EAS AF: 0.560

Gnomad SAS AF: 0.541

Gnomad FIN AF: 0.354

Gnomad MID AF: 0.456

Gnomad NFE AF: 0.399

Gnomad OTH AF: 0.446

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

GnomAD4 genome AF: 0.416 AC: 63188 AN: 152022 Hom.: 13489 Cov.: 32 AF XY: 0.419 AC XY: 31116 AN XY: 74284

Gnomad4 AFR AF: 0.383

Gnomad4 AMR AF: 0.512

Gnomad4 ASJ AF: 0.427

Gnomad4 EAS AF: 0.560

Gnomad4 SAS AF: 0.542

Gnomad4 FIN AF: 0.354

Gnomad4 NFE AF: 0.399

Gnomad4 OTH AF: 0.451

Alfa AF: 0.405 Hom.: 1574

Bravo AF: 0.428

Asia WGS AF: 0.563 AC: 1955 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.91
Cadd	Benign	1.4
Dann	Benign	0.62

Splicing

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

Publications

LitVar

Other links and lift over

dbSNP: rs1668875; hg19: chr8-128341103;