Genetic Variant CASC15:n.1061+25260T>C (chr6-22136180-T-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.1061+25260T>C variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.417 in 152,756 control chromosomes in the GnomAD database, including 13,862 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 0.42 ( 13840 hom., cov: 32)

Exomes 𝑓: 0.21 ( 22 hom. )

Consequence

CASC15
ENST00000444265.6 intron

Scores

Clinical Significance

Not reported in ClinVar

Conservation

PhyloP100: 0.709

Publications

5 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:

Genome browser will be placed here

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=-0.73).

BA1

GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.501 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
NBAT1	NR_034143.1 link	n.717A>G		non_coding_transcript_exon_variant	Exon 3 of 3
CASC15	NR_015410.2 link	n.1422+25260T>C		intron_variant	Intron 9 of 11

Ensembl

Gene	Transcript	HGVSc	Effect	Exon rank	TSL
CASC15	ENST00000444265.6 link	n.1061+25260T>C	intron_variant	Intron 7 of 10	1
NBAT1	ENST00000566912.2 link	n.717A>G	non_coding_transcript_exon_variant	Exon 3 of 3	2
NBAT1	ENST00000823290.1 link	n.558A>G	non_coding_transcript_exon_variant	Exon 2 of 2

Frequencies

GnomAD3 genomes

AF:

0.418

AC:

63550

AN:

151944

Hom.:

13832

Cov.:

show subpopulations

Gnomad AFR

AF:

0.508

Gnomad AMI

AF:

0.519

Gnomad AMR

AF:

0.372

Gnomad ASJ

AF:

0.368

Gnomad EAS

AF:

0.189

Gnomad SAS

AF:

0.462

Gnomad FIN

AF:

0.469

Gnomad MID

AF:

0.465

Gnomad NFE

AF:

0.382

Gnomad OTH

AF:

0.403

GnomAD4 exome

AF:

0.212

AC:

147

AN:

694

Hom.:

Cov.:

AF XY:

0.194

AC XY:

AN XY:

382

show subpopulations

African (AFR)

AF:

0.500

AC:

AN:

American (AMR)

AF:

0.160

AC:

AN:

Ashkenazi Jewish (ASJ)

AF:

0.333

AC:

AN:

East Asian (EAS)

AF:

0.0789

AC:

AN:

South Asian (SAS)

AF:

0.222

AC:

AN:

European-Finnish (FIN)

AF:

0.125

AC:

AN:

Middle Eastern (MID)

AF:

0.250

AC:

AN:

European-Non Finnish (NFE)

AF:

0.221

AC:

114

AN:

516

Other (OTH)

AF:

0.233

AC:

AN:

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.462

Heterozygous variant carriers

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Exome Het

Exome Hom

Variant carriers

<30

30-35

35-40

40-45

45-50

50-55

55-60

60-65

65-70

70-75

75-80

>80

Age

GnomAD4 genome

AF:

0.418

AC:

63584

AN:

152062

Hom.:

13840

Cov.:

AF XY:

0.419

AC XY:

31140

AN XY:

74366

show subpopulations

African (AFR)

AF:

0.507

AC:

21025

AN:

41476

American (AMR)

AF:

0.373

AC:

5691

AN:

15272

Ashkenazi Jewish (ASJ)

AF:

0.368

AC:

1278

AN:

3470

East Asian (EAS)

AF:

0.189

AC:

980

AN:

5178

South Asian (SAS)

AF:

0.460

AC:

2213

AN:

4810

European-Finnish (FIN)

AF:

0.469

AC:

4959

AN:

10572

Middle Eastern (MID)

AF:

0.466

AC:

137

AN:

294

European-Non Finnish (NFE)

AF:

0.382

AC:

25982

AN:

67966

Other (OTH)

AF:

0.401

AC:

846

AN:

2112

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.503

Heterozygous variant carriers

1878

3757

5635

7514

9392

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Genome Het

Genome Hom

Variant carriers

584

1168

1752

2336

2920

<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:

0.388

Hom.:

51160

Bravo

AF:

0.411

Asia WGS

AF:

0.361

AC:

1255

AN:

3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

BayesDel_noAF

Benign

-0.73

CADD

Benign

5.8

(source)

DANN

Benign

0.89

PhyloP100

0.71

Splicing

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

Publications

You must be logged in to view publications. This limit was set because tens of millions (!) of queries from AI bots are generated daily.

Variant summary

Frequency

Consequence

Scores

Clinical Significance

Conservation

Publications

ACMG classification

Transcripts

RefSeq

Ensembl

Frequencies

Age Distribution

Age Distribution

ClinVar

Computational scores

Splicing

Publications

Other links and lift over