chr6-22209381-T-C

Variant names:

• chr6-22209381-T-C
• rs13198653
• ENST00000444265.6:n.1298+4122T>C

Variant summary

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

The ENST00000444265.6(CASC15):​n.1298+4122T>C variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.122 in 152,222 control chromosomes in the GnomAD database, including 1,501 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 0.12 (1501 hom., cov: 32)
• Consequence: CASC15 ENST00000444265.6 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 1.30
• Publications: 2 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]

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=-0.9).
• BA1: GnomAd4 highest subpopulation (SAS) allele frequency at 95% confidence interval = 0.182 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

Ensembl Transcripts

Selected	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	CASC15	ENST00000444265.6	TSL:1	n.1298+4122T>C		intron	N/A
	CASC15	ENST00000561912.3	TSL:5	n.200-46993T>C		intron	N/A
	CASC15	ENST00000567753.2	TSL:6	n.89-4926T>C		intron	N/A

Frequencies

GnomAD3 genomes AF: 0.122 AC: 18516 AN: 152104 Hom.: 1501 Cov.: 32

Gnomad AFR AF: 0.0365

Gnomad AMI AF: 0.109

Gnomad AMR AF: 0.0900

Gnomad ASJ AF: 0.234

Gnomad EAS AF: 0.00520

Gnomad SAS AF: 0.193

Gnomad FIN AF: 0.144

Gnomad MID AF: 0.209

Gnomad NFE AF: 0.175

Gnomad OTH AF: 0.133

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

GnomAD4 genome AF: 0.122 AC: 18511 AN: 152222 Hom.: 1501 Cov.: 32 AF XY: 0.120 AC XY: 8949 AN XY: 74434

African (AFR) AF: 0.0366 AC: 1521 AN: 41558

American (AMR) AF: 0.0899 AC: 1374 AN: 15288

Ashkenazi Jewish (ASJ) AF: 0.234 AC: 814 AN: 3472

East Asian (EAS) AF: 0.00521 AC: 27 AN: 5184

South Asian (SAS) AF: 0.193 AC: 929 AN: 4824

European-Finnish (FIN) AF: 0.144 AC: 1524 AN: 10592

Middle Eastern (MID) AF: 0.197 AC: 58 AN: 294

European-Non Finnish (NFE) AF: 0.175 AC: 11889 AN: 67986

Other (OTH) AF: 0.131 AC: 276 AN: 2112

Alfa AF: 0.164 Hom.: 3012

Bravo AF: 0.112

Asia WGS AF: 0.0920 AC: 320 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.90
CADD	Benign	5.3
DANN	Benign	0.54
PhyloP100		1.3

Splicing

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

Other links and lift over

dbSNP: rs13198653; hg19: chr6-22209610;