dbSNP rs10498707: CASC15:n.1062-104G>C (chr6-22191463-G-C) – ACMG Classification: Benign (-12 pts)

Variant summary

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

The ENST00000444265.6(CASC15):n.1062-104G>C variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0286 in 152,262 control chromosomes in the GnomAD database, including 123 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 0.029 ( 123 hom., cov: 32)

Exomes 𝑓: 0.0 ( 0 hom. )

Failed GnomAD Quality Control

Consequence

CASC15
ENST00000444265.6 intron

Scores

Clinical Significance

Not reported in ClinVar

Conservation

PhyloP100: 0.617

Publications

0 publications found

Variant links:

Genes affected

CASC15 (HGNC:28245): (cancer susceptibility 15) This gene produces a long non-coding RNA that may regulate cell proliferation. This RNA is upregulated in hepatocellular carcinoma, where it is thought to function as an oncogene. However, some splice variants of this gene may function as a tumor suppressor in neuroblastoma and other tumor types. Circular RNA variants were observed at this gene. [provided by RefSeq, Dec 2017]

CASC15 links:

NBAT1 (HGNC:49075): (neuroblastoma associated transcript 1)

NBAT1 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=-0.81).

BA1

GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.126 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
CASC15	NR_015410.2 link	n.1488-104G>C		intron_variant	Intron 10 of 11

Ensembl

Gene	Transcript	HGVSc	Effect	Exon rank	TSL
CASC15	ENST00000444265.6 link	n.1062-104G>C	intron_variant	Intron 7 of 10	1
CASC15	ENST00000561912.3 link	n.199+44393G>C	intron_variant	Intron 1 of 10	5
CASC15	ENST00000567753.2 link	n.89-22844G>C	intron_variant	Intron 1 of 2	6

Frequencies

GnomAD3 genomes

AF:

0.0285

AC:

4339

AN:

152144

Hom.:

120

Cov.:

show subpopulations

Gnomad AFR

AF:

0.0386

Gnomad AMI

AF:

0.0846

Gnomad AMR

AF:

0.0161

Gnomad ASJ

AF:

0.0135

Gnomad EAS

AF:

0.133

Gnomad SAS

AF:

0.0597

Gnomad FIN

AF:

0.0137

Gnomad MID

AF:

0.0285

Gnomad NFE

AF:

0.0176

Gnomad OTH

AF:

0.0197

GnomAD4 exome

Data not reliable, filtered out with message: AC0

AF:

0.00

AC:

AN:

Hom.:

AF XY:

0.00

AC XY:

AN XY:

African (AFR)

AC:

AN:

American (AMR)

AC:

AN:

Ashkenazi Jewish (ASJ)

AC:

AN:

East Asian (EAS)

AF:

0.00

AC:

AN:

South Asian (SAS)

AC:

AN:

European-Finnish (FIN)

AC:

AN:

Middle Eastern (MID)

AC:

AN:

European-Non Finnish (NFE)

AF:

0.00

AC:

AN:

Other (OTH)

AC:

AN:

GnomAD4 genome

AF:

0.0286

AC:

4348

AN:

152262

Hom.:

123

Cov.:

AF XY:

0.0297

AC XY:

2208

AN XY:

74434

show subpopulations

African (AFR)

AF:

0.0386

AC:

1605

AN:

41566

American (AMR)

AF:

0.0161

AC:

246

AN:

15294

Ashkenazi Jewish (ASJ)

AF:

0.0135

AC:

AN:

3470

East Asian (EAS)

AF:

0.134

AC:

691

AN:

5158

South Asian (SAS)

AF:

0.0595

AC:

287

AN:

4820

European-Finnish (FIN)

AF:

0.0137

AC:

145

AN:

10616

Middle Eastern (MID)

AF:

0.0238

AC:

AN:

294

European-Non Finnish (NFE)

AF:

0.0176

AC:

1199

AN:

68026

Other (OTH)

AF:

0.0209

AC:

AN:

2108

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.502

Heterozygous variant carriers

215

430

646

861

1076

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Genome Het

Genome Hom

Variant carriers

120

180

240

300

<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:

0.0191

Hom.:

Bravo

AF:

0.0289

Asia WGS

AF:

0.0920

AC:

320

AN:

3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

BayesDel_noAF

Benign

-0.81

CADD

Benign

1.6

(source)

DANN

Benign

0.56

PhyloP100

0.62

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

Transcripts

RefSeq

Ensembl

Frequencies

Age Distribution

ClinVar

Computational scores

Splicing

Publications

Other links and lift over