rs13249993

Variant names:

• chr8-127338270-G-A
• rs13249993
• ENST00000501396.6:n.547-15116C>T

Your query was ambiguous. Multiple possible variants found:

• chr8-127338270-G-A
• chr8-127338270-G-C

Variant summary

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

The ENST00000501396.6(CASC8):​n.547-15116C>T variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.588 in 151,998 control chromosomes in the GnomAD database, including 26,524 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 0.59 (26524 hom., cov: 32)
• Consequence: CASC8 ENST00000501396.6 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.206
• Publications: 7 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=-0.95).
• BA1: GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.686 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
CASC21	NR_117099.1	n.303-1011G>A		intron_variant	Intron 2 of 3
CASC8	NR_117100.1	n.1177-48210C>T		intron_variant	Intron 5 of 5

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
CASC8	ENST00000501396.6	n.547-15116C>T		intron_variant	Intron 1 of 2	1
CASC8	ENST00000502082.5	n.1177-48210C>T		intron_variant	Intron 5 of 5	1
CASC8	ENST00000523825.3	n.547-48210C>T		intron_variant	Intron 1 of 1	1

Frequencies

GnomAD3 genomes AF: 0.588 AC: 89311 AN: 151880 Hom.: 26474 Cov.: 32

Gnomad AFR AF: 0.599

Gnomad AMI AF: 0.697

Gnomad AMR AF: 0.696

Gnomad ASJ AF: 0.497

Gnomad EAS AF: 0.705

Gnomad SAS AF: 0.679

Gnomad FIN AF: 0.534

Gnomad MID AF: 0.604

Gnomad NFE AF: 0.553

Gnomad OTH AF: 0.613

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

GnomAD4 genome AF: 0.588 AC: 89419 AN: 151998 Hom.: 26524 Cov.: 32 AF XY: 0.595 AC XY: 44169 AN XY: 74296

African (AFR) AF: 0.600 AC: 24854 AN: 41456

American (AMR) AF: 0.697 AC: 10639 AN: 15272

Ashkenazi Jewish (ASJ) AF: 0.497 AC: 1723 AN: 3466

East Asian (EAS) AF: 0.705 AC: 3620 AN: 5136

South Asian (SAS) AF: 0.679 AC: 3269 AN: 4814

European-Finnish (FIN) AF: 0.534 AC: 5641 AN: 10572

Middle Eastern (MID) AF: 0.612 AC: 180 AN: 294

European-Non Finnish (NFE) AF: 0.553 AC: 37565 AN: 67966

Other (OTH) AF: 0.612 AC: 1292 AN: 2110

Alfa AF: 0.568 Hom.: 17155

Bravo AF: 0.598

Asia WGS AF: 0.694 AC: 2411 AN: 3476

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.95
CADD	Benign	1.2
DANN	Benign	0.50
PhyloP100		-0.21

Splicing

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

Other links and lift over

dbSNP: rs13249993; hg19: chr8-128350515;