rs10507198

Variant names:

• chr12-105707400-G-A
• rs10507198
• ENST00000547465.1:n.83+544G>A

Variant summary

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

The ENST00000547465.1(CASC18):​n.83+544G>A variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.32 in 151,946 control chromosomes in the GnomAD database, including 8,025 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 0.32 (8025 hom., cov: 32)
• Consequence: CASC18 ENST00000547465.1 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 0.00300
• Publications: 6 publications found

Genes affected

CASC18 (HGNC:49463): (cancer susceptibility 18)

ENSG00000300812 (HGNC:):

ACMG classification

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

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.97).
• BA1: GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.404 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
CASC18	NR_110108.1	n.54+3144G>A		intron_variant	Intron 1 of 2
CASC18	NR_110109.1	n.54+3144G>A		intron_variant	Intron 1 of 4
CASC18	NR_110110.1	n.83+544G>A		intron_variant	Intron 1 of 2

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
CASC18	ENST00000547465.1	n.83+544G>A		intron_variant	Intron 1 of 1	1
CASC18	ENST00000548557.1	n.54+3144G>A		intron_variant	Intron 1 of 2	1
CASC18	ENST00000656319.1	n.144+2002G>A		intron_variant	Intron 1 of 2

Frequencies

GnomAD3 genomes AF: 0.320 AC: 48553 AN: 151828 Hom.: 8008 Cov.: 32

Gnomad AFR AF: 0.409

Gnomad AMI AF: 0.238

Gnomad AMR AF: 0.284

Gnomad ASJ AF: 0.359

Gnomad EAS AF: 0.366

Gnomad SAS AF: 0.227

Gnomad FIN AF: 0.257

Gnomad MID AF: 0.268

Gnomad NFE AF: 0.285

Gnomad OTH AF: 0.335

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

GnomAD4 genome AF: 0.320 AC: 48600 AN: 151946 Hom.: 8025 Cov.: 32 AF XY: 0.315 AC XY: 23410 AN XY: 74262

African (AFR) AF: 0.409 AC: 16932 AN: 41406

American (AMR) AF: 0.284 AC: 4339 AN: 15270

Ashkenazi Jewish (ASJ) AF: 0.359 AC: 1244 AN: 3468

East Asian (EAS) AF: 0.366 AC: 1892 AN: 5164

South Asian (SAS) AF: 0.227 AC: 1092 AN: 4810

European-Finnish (FIN) AF: 0.257 AC: 2710 AN: 10546

Middle Eastern (MID) AF: 0.264 AC: 77 AN: 292

European-Non Finnish (NFE) AF: 0.285 AC: 19396 AN: 67968

Other (OTH) AF: 0.332 AC: 701 AN: 2112

Alfa AF: 0.301 Hom.: 29917

Bravo AF: 0.329

Asia WGS AF: 0.300 AC: 1043 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.97
CADD	Benign	1.7
DANN	Benign	0.73
PhyloP100		0.0030

Splicing

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

Other links and lift over

dbSNP: rs10507198; hg19: chr12-106101178;