dbSNP rs924993: CASC8:n.687-2194C>T (chr8-127292254-G-A) – ACMG Classification: Benign (-12 pts)

Variant summary

Our verdict is Benign. The variant received -12 ACMG points: 0P and 12B. BP4_StrongBA1

The ENST00000605028.1(ENSG00000271509):n.22G>A 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 0.0507 in 152,166 control chromosomes in the GnomAD database, including 447 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 0.051 ( 447 hom., cov: 32)

Exomes 𝑓: 0.17 ( 0 hom. )

Consequence

ENSG00000271509
ENST00000605028.1 non_coding_transcript_exon

Scores

Clinical Significance

Not reported in ClinVar

Conservation

PhyloP100: -0.00700

Publications

1 publications found

Variant links:

Genes affected

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

CASC8 links:

ENSG00000271509 (HGNC:):

ENSG00000271509 links:

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]

PCAT1 links:

CASC21 (HGNC:49836): (cancer susceptibility 21)

CASC21 links:

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ACMG classification

Classification was made for transcript

Our verdict: Benign. The variant received -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 = 0.271 is higher than 0.05.

Variant Effect in Transcripts

ACMG analysis was done for transcript: ENST00000605028.1. 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.149-29819G>A		intron	N/A
	CASC8	NR_117100.1		n.1177-2194C>T		intron	N/A

Ensembl Transcripts

Gene	Transcript	Tags	HGVSc	Effect	Exon Rank
CASC8	ENST00000501396.6	TSL:1	n.687-2194C>T	intron	N/A
CASC8	ENST00000502082.5	TSL:1	n.1177-2194C>T	intron	N/A
CASC8	ENST00000523825.3	TSL:1	n.547-2194C>T	intron	N/A

Frequencies

GnomAD3 genomes

AF:

0.0506

AC:

7692

AN:

152042

Hom.:

442

Cov.:

show subpopulations

Gnomad AFR

AF:

0.0548

Gnomad AMI

AF:

0.0714

Gnomad AMR

AF:

0.117

Gnomad ASJ

AF:

0.0338

Gnomad EAS

AF:

0.283

Gnomad SAS

AF:

0.0964

Gnomad FIN

AF:

0.0440

Gnomad MID

AF:

0.0380

Gnomad NFE

AF:

0.0136

Gnomad OTH

AF:

0.0583

GnomAD4 exome

AF:

0.167

AC:

AN:

Hom.:

Cov.:

AF XY:

0.00

AC XY:

AN XY:

show subpopulations

African (AFR)

AC:

AN:

American (AMR)

AC:

AN:

Ashkenazi Jewish (ASJ)

AC:

AN:

East Asian (EAS)

AC:

AN:

South Asian (SAS)

AC:

AN:

European-Finnish (FIN)

AC:

AN:

Middle Eastern (MID)

AC:

AN:

European-Non Finnish (NFE)

AF:

0.167

AC:

AN:

Other (OTH)

AC:

AN:

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.575

Heterozygous variant carriers

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

GnomAD4 genome

AF:

0.0507

AC:

7712

AN:

152160

Hom.:

447

Cov.:

AF XY:

0.0561

AC XY:

4173

AN XY:

74378

show subpopulations

African (AFR)

AF:

0.0547

AC:

2270

AN:

41498

American (AMR)

AF:

0.118

AC:

1798

AN:

15282

Ashkenazi Jewish (ASJ)

AF:

0.0338

AC:

117

AN:

3466

East Asian (EAS)

AF:

0.283

AC:

1466

AN:

5178

South Asian (SAS)

AF:

0.0969

AC:

466

AN:

4810

European-Finnish (FIN)

AF:

0.0440

AC:

466

AN:

10598

Middle Eastern (MID)

AF:

0.0374

AC:

AN:

294

European-Non Finnish (NFE)

AF:

0.0136

AC:

927

AN:

68010

Other (OTH)

AF:

0.0596

AC:

126

AN:

2114

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.502

Heterozygous variant carriers

364

728

1093

1457

1821

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Genome Het

Genome Hom

Variant carriers

184

276

368

460

<30

30-35

35-40

40-45

45-50

50-55

55-60

60-65

65-70

70-75

75-80

>80

Age

Alfa

AF:

0.0309

Hom.:

674

Bravo

AF:

0.0608

Asia WGS

AF:

0.204

AC:

705

AN:

3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name

Calibrated prediction

Score

Prediction

BayesDel_noAF

Benign

-0.91

CADD

Benign

2.2

(source)

DANN

Benign

0.40

PhyloP100

-0.0070

Splicing

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

Publications

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Variant summary

Frequency

Consequence

Scores

Clinical Significance

Conservation

Publications

ACMG classification

Variant Effect in Transcripts

RefSeq Transcripts

Ensembl Transcripts

Frequencies

Age Distribution

ClinVar

Computational scores

Splicing

Publications

Other links and lift over