rs1021955

Variant names:

• chr8-127191728-A-G
• rs1021955
• ENST00000641060.1:n.442T>C

Your query was ambiguous. Multiple possible variants found:

• chr8-127191728-A-G
• chr8-127191728-A-T

Variant summary

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

The ENST00000641060.1(CASC19):​n.442T>C variant causes a non coding transcript exon change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.461 in 151,950 control chromosomes in the GnomAD database, including 17,657 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 0.46 (17657 hom., cov: 31)
  • Exomes 𝑓: 0.0 (0 hom.)
  • Failed GnomAD Quality Control
• Consequence: CASC19 ENST00000641060.1 non_coding_transcript_exon
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 0.749
• Publications: 7 publications found

Genes affected

CASC19 (HGNC:49476): (cancer susceptibility 19)

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=-0.84).
• BA1: GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.67 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
CASC19	NR_120364.1	n.154-3613T>C		intron_variant	Intron 1 of 2

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
CASC19	ENST00000641060.1	n.442T>C		non_coding_transcript_exon_variant	Exon 5 of 7
CASC19	ENST00000641674.2	n.538T>C		non_coding_transcript_exon_variant	Exon 5 of 9
CASC19	ENST00000642082.1	n.588T>C		non_coding_transcript_exon_variant	Exon 1 of 4

Frequencies

GnomAD3 genomes AF: 0.460 AC: 69886 AN: 151830 Hom.: 17619 Cov.: 31

Gnomad AFR AF: 0.677

Gnomad AMI AF: 0.440

Gnomad AMR AF: 0.425

Gnomad ASJ AF: 0.332

Gnomad EAS AF: 0.451

Gnomad SAS AF: 0.292

Gnomad FIN AF: 0.339

Gnomad MID AF: 0.291

Gnomad NFE AF: 0.377

Gnomad OTH AF: 0.422

GnomAD4 exome Data not reliable, filtered out with message: AC0 AF: 0.00 AC: 0 AN: 2 Hom.: 0 Cov.: 0 AF XY: 0.00 AC XY: 0 AN XY: 2

African (AFR) AC: 0 AN: 0

American (AMR) AC: 0 AN: 0

Ashkenazi Jewish (ASJ) AC: 0 AN: 0

East Asian (EAS) AC: 0 AN: 0

South Asian (SAS) AF: 0.00 AC: 0 AN: 2

European-Finnish (FIN) AC: 0 AN: 0

Middle Eastern (MID) AC: 0 AN: 0

European-Non Finnish (NFE) AC: 0 AN: 0

Other (OTH) AC: 0 AN: 0

GnomAD4 genome AF: 0.461 AC: 69977 AN: 151950 Hom.: 17657 Cov.: 31 AF XY: 0.454 AC XY: 33723 AN XY: 74248

African (AFR) AF: 0.677 AC: 28058 AN: 41466

American (AMR) AF: 0.426 AC: 6493 AN: 15256

Ashkenazi Jewish (ASJ) AF: 0.332 AC: 1152 AN: 3470

East Asian (EAS) AF: 0.450 AC: 2321 AN: 5154

South Asian (SAS) AF: 0.291 AC: 1398 AN: 4812

European-Finnish (FIN) AF: 0.339 AC: 3575 AN: 10552

Middle Eastern (MID) AF: 0.296 AC: 87 AN: 294

European-Non Finnish (NFE) AF: 0.377 AC: 25598 AN: 67922

Other (OTH) AF: 0.423 AC: 894 AN: 2112

Alfa AF: 0.421 Hom.: 4739

Bravo AF: 0.479

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.84
CADD	Benign	4.3
DANN	Benign	0.57
PhyloP100		0.75
RBP_binding_hub_radar		0.0
RBP_regulation_power_radar		1.1

Splicing

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

Other links and lift over

dbSNP: rs1021955; hg19: chr8-128203973;