Genetic Variant ENST00000561912.3:n.200-35743C>T (chr6-22220631-C-T) – ACMG Classification: Benign (-12 pts)

Variant summary

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

The ENST00000561912.3(CASC15):n.200-35743C>T variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.226 in 151,678 control chromosomes in the GnomAD database, including 5,804 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 0.23 ( 5803 hom., cov: 30)

Exomes 𝑓: 0.060 ( 1 hom. )

Consequence

CASC15
ENST00000561912.3 intron

Scores

Clinical Significance

Not reported in ClinVar

Conservation

PhyloP100: 1.50

Publications

4 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=-0.85).

BA1

GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.498 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt

Ensembl

Gene	Transcript	HGVSc	Effect	Exon rank	TSL
CASC15	ENST00000561912.3 link	n.200-35743C>T	intron_variant	Intron 1 of 10	5
CASC15	ENST00000567753.2 link	n.1485-962C>T	intron_variant	Intron 2 of 2	6
CASC15	ENST00000636388.1 link	n.310-962C>T	intron_variant	Intron 2 of 2	5

Frequencies

GnomAD3 genomes

AF:

0.226

AC:

34200

AN:

151512

Hom.:

5785

Cov.:

show subpopulations

Gnomad AFR

AF:

0.456

Gnomad AMI

AF:

0.242

Gnomad AMR

AF:

0.185

Gnomad ASJ

AF:

0.0914

Gnomad EAS

AF:

0.515

Gnomad SAS

AF:

0.162

Gnomad FIN

AF:

0.119

Gnomad MID

AF:

0.152

Gnomad NFE

AF:

0.103

Gnomad OTH

AF:

0.197

GnomAD4 exome

AF:

0.0600

AC:

AN:

Hom.:

AF XY:

0.0278

AC XY:

AN XY:

show subpopulations

African (AFR)

AF:

0.500

AC:

AN:

American (AMR)

AF:

0.00

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)

AF:

0.00

AC:

AN:

European-Non Finnish (NFE)

AF:

0.00

AC:

AN:

Other (OTH)

AF:

0.500

AC:

AN:

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.525

Heterozygous variant carriers

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

GnomAD4 genome

AF:

0.226

AC:

34266

AN:

151628

Hom.:

5803

Cov.:

AF XY:

0.226

AC XY:

16722

AN XY:

74106

show subpopulations

African (AFR)

AF:

0.456

AC:

18809

AN:

41264

American (AMR)

AF:

0.185

AC:

2817

AN:

15254

Ashkenazi Jewish (ASJ)

AF:

0.0914

AC:

317

AN:

3468

East Asian (EAS)

AF:

0.515

AC:

2619

AN:

5090

South Asian (SAS)

AF:

0.162

AC:

780

AN:

4808

European-Finnish (FIN)

AF:

0.119

AC:

1258

AN:

10546

Middle Eastern (MID)

AF:

0.153

AC:

AN:

294

European-Non Finnish (NFE)

AF:

0.103

AC:

6986

AN:

67892

Other (OTH)

AF:

0.197

AC:

414

AN:

2100

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.501

Heterozygous variant carriers

1108

2216

3323

4431

5539

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Genome Het

Genome Hom

Variant carriers

332

664

996

1328

1660

<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:

0.148

Hom.:

8011

Bravo

AF:

0.244

Asia WGS

AF:

0.316

AC:

1098

AN:

3474

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

BayesDel_noAF

Benign

-0.85

CADD

Benign

7.2

(source)

DANN

Benign

0.80

PhyloP100

1.5

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