6-22201365-C-T

Variant names:

• chr6-22201365-C-T
• rs7751843
• ENST00000444265.6:n.1224-3820C>T

Variant summary

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

The ENST00000444265.6(CASC15):​n.1224-3820C>T variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0805 in 152,124 control chromosomes in the GnomAD database, including 582 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 0.081 (582 hom., cov: 32)
• Consequence: CASC15 ENST00000444265.6 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 0.0730
• Publications: 3 publications found

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]

LOC124901275 (HGNC:):

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

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 (AMR) allele frequency at 95% confidence interval = 0.0873 is higher than 0.05.

Variant Effect in Transcripts

ACMG analysis was done for transcript: ENST00000444265.6. You can select a different transcript below to see updated ACMG assignments.

RefSeq Transcripts

Selected	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
There are no transcript annotations for this variant.

Ensembl Transcripts

Selected	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	CASC15	ENST00000444265.6	TSL:1	n.1224-3820C>T		intron	N/A
	CASC15	ENST00000561912.3	TSL:5	n.199+54295C>T		intron	N/A
	CASC15	ENST00000567753.2	TSL:6	n.89-12942C>T		intron	N/A

Frequencies

GnomAD3 genomes AF: 0.0805 AC: 12241 AN: 152006 Hom.: 581 Cov.: 32

Gnomad AFR AF: 0.0476

Gnomad AMI AF: 0.162

Gnomad AMR AF: 0.0913

Gnomad ASJ AF: 0.0320

Gnomad EAS AF: 0.0768

Gnomad SAS AF: 0.0699

Gnomad FIN AF: 0.178

Gnomad MID AF: 0.0570

Gnomad NFE AF: 0.0856

Gnomad OTH AF: 0.0786

We have no GnomAD4 exomes data on this position. Probably position not covered by the project.

GnomAD4 genome AF: 0.0805 AC: 12249 AN: 152124 Hom.: 582 Cov.: 32 AF XY: 0.0844 AC XY: 6278 AN XY: 74348

African (AFR) AF: 0.0476 AC: 1974 AN: 41500

American (AMR) AF: 0.0913 AC: 1395 AN: 15278

Ashkenazi Jewish (ASJ) AF: 0.0320 AC: 111 AN: 3472

East Asian (EAS) AF: 0.0770 AC: 399 AN: 5180

South Asian (SAS) AF: 0.0703 AC: 339 AN: 4820

European-Finnish (FIN) AF: 0.178 AC: 1881 AN: 10570

Middle Eastern (MID) AF: 0.0578 AC: 17 AN: 294

European-Non Finnish (NFE) AF: 0.0856 AC: 5821 AN: 67994

Other (OTH) AF: 0.0783 AC: 165 AN: 2108

Alfa AF: 0.0779 Hom.: 596

Bravo AF: 0.0715

Asia WGS AF: 0.0720 AC: 252 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.84
CADD	Benign	5.8
DANN	Benign	0.51
PhyloP100		0.073

Splicing

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

Other links and lift over

dbSNP: rs7751843; hg19: chr6-22201594;