rs13249993

Positions:

• chr8-127338270-G-A
• chr8-127338270-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.303-1011G>A 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 0.588 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: CASC21 NR_117099.1 intron, non_coding_transcript
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.206

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=-0.95).
• 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/exons	MANE	UniProt
CASC21	NR_117099.1	n.303-1011G>A		intron_variant, non_coding_transcript_variant
CASC8	NR_117100.1	n.1177-48210C>T		intron_variant, non_coding_transcript_variant

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
CASC8	ENST00000502082.5	n.1177-48210C>T		intron_variant, non_coding_transcript_variant		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

Gnomad4 AFR AF: 0.600

Gnomad4 AMR AF: 0.697

Gnomad4 ASJ AF: 0.497

Gnomad4 EAS AF: 0.705

Gnomad4 SAS AF: 0.679

Gnomad4 FIN AF: 0.534

Gnomad4 NFE AF: 0.553

Gnomad4 OTH AF: 0.612

Alfa AF: 0.573 Hom.: 10613

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

Splicing

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

Publications

LitVar

Other links and lift over

dbSNP: rs13249993; hg19: chr8-128350515;