chr8-127279333-C-T

Variant names:

• chr8-127279333-C-T
• rs4871780
• ENST00000644021.1:n.148+34549C>T

Variant summary

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

The NR_117099.1(CASC21):​n.148+34549C>T variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.315 in 152,122 control chromosomes in the GnomAD database, including 8,933 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 0.32 (8933 hom., cov: 32)
• Consequence: CASC21 NR_117099.1 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 0.0970
• Publications: 7 publications found

Genes affected

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]

ENSG00000287781 (HGNC:):

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=-0.93).
• BA1: GnomAd4 highest subpopulation (NFE) allele frequency at 95% confidence interval = 0.43 is higher than 0.05.

Variant Effect in Transcripts

ACMG analysis was done for transcript: NR_117099.1. You can select a different transcript below to see updated ACMG assignments.

RefSeq Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	CASC21	NR_117099.1		n.148+34549C>T		intron	N/A

Ensembl Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	PCAT1	ENST00000644021.1		n.148+34549C>T		intron	N/A
	PCAT1	ENST00000645463.1		n.856-13479C>T		intron	N/A
	PCAT1	ENST00000646670.1		n.1065-59948C>T		intron	N/A

Frequencies

GnomAD3 genomes AF: 0.315 AC: 47951 AN: 152004 Hom.: 8941 Cov.: 32

Gnomad AFR AF: 0.152

Gnomad AMI AF: 0.231

Gnomad AMR AF: 0.284

Gnomad ASJ AF: 0.471

Gnomad EAS AF: 0.0652

Gnomad SAS AF: 0.199

Gnomad FIN AF: 0.367

Gnomad MID AF: 0.405

Gnomad NFE AF: 0.434

Gnomad OTH AF: 0.343

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

GnomAD4 genome AF: 0.315 AC: 47950 AN: 152122 Hom.: 8933 Cov.: 32 AF XY: 0.306 AC XY: 22741 AN XY: 74374

African (AFR) AF: 0.152 AC: 6293 AN: 41524

American (AMR) AF: 0.283 AC: 4323 AN: 15272

Ashkenazi Jewish (ASJ) AF: 0.471 AC: 1632 AN: 3468

East Asian (EAS) AF: 0.0653 AC: 339 AN: 5188

South Asian (SAS) AF: 0.201 AC: 969 AN: 4824

European-Finnish (FIN) AF: 0.367 AC: 3880 AN: 10580

Middle Eastern (MID) AF: 0.395 AC: 116 AN: 294

European-Non Finnish (NFE) AF: 0.434 AC: 29471 AN: 67950

Other (OTH) AF: 0.339 AC: 716 AN: 2110

Alfa AF: 0.365 Hom.: 7324

Bravo AF: 0.301

Asia WGS AF: 0.139 AC: 484 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.93
CADD	Benign	3.3
DANN	Benign	0.38
PhyloP100		0.097

Splicing

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

Other links and lift over

dbSNP: rs4871780; hg19: chr8-128291578;