rs10219670

Positions:

• chr12-105714941-C-A

Variant summary

Our verdict is Benign. Variant got -12 ACMG points: 0P and 12B. BP4_Strong BA1

The NR_110109.1(CASC18):​n.55-221C>A variant causes a intron, non coding transcript change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.604 in 152,012 control chromosomes in the GnomAD database, including 28,052 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 0.60 (28052 hom., cov: 32)
• Consequence: CASC18 NR_110109.1 intron, non_coding_transcript
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.259

Genes affected

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

ACMG classification

Verdict is Benign. Variant got -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 = 0.67 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
CASC18	NR_110109.1	n.55-221C>A		intron_variant, non_coding_transcript_variant
CASC18	NR_110108.1	n.54+10685C>A		intron_variant, non_coding_transcript_variant
CASC18	NR_110110.1	n.83+8085C>A		intron_variant, non_coding_transcript_variant
CASC18	NR_110111.2	n.83+8085C>A		intron_variant, non_coding_transcript_variant

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
CASC18	ENST00000547465.1	n.83+8085C>A		intron_variant, non_coding_transcript_variant		1
CASC18	ENST00000548557.1	n.54+10685C>A		intron_variant, non_coding_transcript_variant		1
CASC18	ENST00000656319.1	n.144+9543C>A		intron_variant, non_coding_transcript_variant

Frequencies

GnomAD3 genomes AF: 0.604 AC: 91700 AN: 151894 Hom.: 28011 Cov.: 32

Gnomad AFR AF: 0.676

Gnomad AMI AF: 0.677

Gnomad AMR AF: 0.662

Gnomad ASJ AF: 0.730

Gnomad EAS AF: 0.546

Gnomad SAS AF: 0.385

Gnomad FIN AF: 0.481

Gnomad MID AF: 0.658

Gnomad NFE AF: 0.577

Gnomad OTH AF: 0.627

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

GnomAD4 genome AF: 0.604 AC: 91799 AN: 152012 Hom.: 28052 Cov.: 32 AF XY: 0.597 AC XY: 44314 AN XY: 74286

Gnomad4 AFR AF: 0.676

Gnomad4 AMR AF: 0.663

Gnomad4 ASJ AF: 0.730

Gnomad4 EAS AF: 0.546

Gnomad4 SAS AF: 0.386

Gnomad4 FIN AF: 0.481

Gnomad4 NFE AF: 0.577

Gnomad4 OTH AF: 0.623

Alfa AF: 0.601 Hom.: 4282

Bravo AF: 0.627

Asia WGS AF: 0.494 AC: 1721 AN: 3476

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.97
CADD	Benign	0.46
DANN	Benign	0.62

Splicing

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

Publications

LitVar

Other links and lift over

dbSNP: rs10219670; hg19: chr12-106108719;