rs10498703

Variant names:

• chr6-22018598-G-A
• rs10498703
• ENST00000444265.6:n.318-1741G>A

Your query was ambiguous. Multiple possible variants found:

• chr6-22018598-G-A
• chr6-22018598-G-C

Variant summary

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

The ENST00000444265.6(CASC15):​n.318-1741G>A variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.131 in 151,932 control chromosomes in the GnomAD database, including 1,900 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 0.13 (1900 hom., cov: 32)
• Consequence: CASC15 ENST00000444265.6 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 0.174
• 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]

ACMG classification

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

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.86).
• BA1: GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.457 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
CASC15	NR_015410.2	n.900-1741G>A		intron_variant	Intron 6 of 11

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
CASC15	ENST00000444265.6	n.318-1741G>A		intron_variant	Intron 3 of 10	1
CASC15	ENST00000606851.5	n.869-1741G>A		intron_variant	Intron 6 of 11	2
CASC15	ENST00000607048.5	n.495-1741G>A		intron_variant	Intron 5 of 11	2

Frequencies

GnomAD3 genomes AF: 0.131 AC: 19884 AN: 151814 Hom.: 1892 Cov.: 32

Gnomad AFR AF: 0.125

Gnomad AMI AF: 0.0901

Gnomad AMR AF: 0.235

Gnomad ASJ AF: 0.123

Gnomad EAS AF: 0.472

Gnomad SAS AF: 0.184

Gnomad FIN AF: 0.0932

Gnomad MID AF: 0.101

Gnomad NFE AF: 0.0888

Gnomad OTH AF: 0.131

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

GnomAD4 genome AF: 0.131 AC: 19916 AN: 151932 Hom.: 1900 Cov.: 32 AF XY: 0.136 AC XY: 10108 AN XY: 74240

African (AFR) AF: 0.125 AC: 5179 AN: 41470

American (AMR) AF: 0.236 AC: 3594 AN: 15250

Ashkenazi Jewish (ASJ) AF: 0.123 AC: 426 AN: 3456

East Asian (EAS) AF: 0.473 AC: 2427 AN: 5132

South Asian (SAS) AF: 0.184 AC: 881 AN: 4800

European-Finnish (FIN) AF: 0.0932 AC: 983 AN: 10548

Middle Eastern (MID) AF: 0.112 AC: 33 AN: 294

European-Non Finnish (NFE) AF: 0.0888 AC: 6034 AN: 67964

Other (OTH) AF: 0.131 AC: 277 AN: 2108

Alfa AF: 0.130 Hom.: 774

Bravo AF: 0.146

Asia WGS AF: 0.306 AC: 1063 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.86
CADD	Benign	3.7
DANN	Benign	0.61
PhyloP100		0.17

Splicing

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

Other links and lift over

dbSNP: rs10498703; hg19: chr6-22018827;