6-22362531-A-G

Variant names:

• chr6-22362531-A-G
• rs1205923
• ENST00000561912.3:n.1348-5683A>G

Variant summary

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

The ENST00000561912.3(CASC15):​n.1348-5683A>G variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.575 in 151,952 control chromosomes in the GnomAD database, including 25,096 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 0.57 (25096 hom., cov: 31)
• Consequence: CASC15 ENST00000561912.3 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 0.466
• Publications: 1 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]

LOC105374971 (HGNC:):

ACMG classification

Our verdict: Benign. The variant received -12 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.93).
• BA1: GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.642 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
LOC105374971	XR_001744023.2	n.368-5683A>G		intron_variant	Intron 2 of 3
LOC105374971	XR_001744024.2	n.367+9880A>G		intron_variant	Intron 2 of 4

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
CASC15	ENST00000561912.3	n.1348-5683A>G		intron_variant	Intron 10 of 10	5
CASC15	ENST00000652081.2	n.145+9880A>G		intron_variant	Intron 2 of 7
CASC15	ENST00000846434.1	n.346+9880A>G		intron_variant	Intron 2 of 5

Frequencies

GnomAD3 genomes AF: 0.575 AC: 87236 AN: 151834 Hom.: 25060 Cov.: 31

Gnomad AFR AF: 0.618

Gnomad AMI AF: 0.563

Gnomad AMR AF: 0.538

Gnomad ASJ AF: 0.551

Gnomad EAS AF: 0.661

Gnomad SAS AF: 0.536

Gnomad FIN AF: 0.543

Gnomad MID AF: 0.601

Gnomad NFE AF: 0.559

Gnomad OTH AF: 0.558

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

GnomAD4 genome AF: 0.575 AC: 87330 AN: 151952 Hom.: 25096 Cov.: 31 AF XY: 0.574 AC XY: 42603 AN XY: 74252

African (AFR) AF: 0.618 AC: 25611 AN: 41426

American (AMR) AF: 0.538 AC: 8227 AN: 15278

Ashkenazi Jewish (ASJ) AF: 0.551 AC: 1913 AN: 3470

East Asian (EAS) AF: 0.661 AC: 3399 AN: 5144

South Asian (SAS) AF: 0.537 AC: 2586 AN: 4816

European-Finnish (FIN) AF: 0.543 AC: 5734 AN: 10554

Middle Eastern (MID) AF: 0.595 AC: 175 AN: 294

European-Non Finnish (NFE) AF: 0.559 AC: 37991 AN: 67948

Other (OTH) AF: 0.560 AC: 1183 AN: 2114

Alfa AF: 0.562 Hom.: 3094

Bravo AF: 0.576

Asia WGS AF: 0.588 AC: 2045 AN: 3476

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.93
CADD	Benign	12
DANN	Benign	0.59
PhyloP100		0.47

Splicing

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

Other links and lift over

dbSNP: rs1205923; hg19: chr6-22362760;