rs10956372

chr8-127458011-T-Achr8-127458011-T-C

Variant summary

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

The NR_117100.1(CASC8):n.1041+21072A>T 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 0.537 in 152,098 control chromosomes in the GnomAD database, including 25,232 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 0.54 (25232 hom., cov: 32)
• Consequence: CASC8 NR_117100.1 intron, non_coding_transcript
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.0100

Genes affected

CASC8 (HGNC:45129): (cancer susceptibility 8)

ACMG classification

Verdict is Benign. Variant got -12 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.88).
• BA1: GnomAd4 highest subpopulation (NFE) allele frequency at 95% confidence interval = 0.676 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
CASC8	NR_117100.1	n.1041+21072A>T		intron_variant, non_coding_transcript_variant
CASC8	NR_024393.1	n.1042-14291A>T		intron_variant, non_coding_transcript_variant

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
CASC8	ENST00000502056.1	n.1042-14291A>T		intron_variant, non_coding_transcript_variant		1
CASC8	ENST00000502082.5	n.1041+21072A>T		intron_variant, non_coding_transcript_variant		1

Frequencies

GnomAD3 genomes AF: 0.538 AC: 81703 AN: 151980 Hom.: 25232 Cov.: 32

Gnomad AFR AF: 0.209

Gnomad AMI AF: 0.771

Gnomad AMR AF: 0.654

Gnomad ASJ AF: 0.646

Gnomad EAS AF: 0.532

Gnomad SAS AF: 0.653

Gnomad FIN AF: 0.617

Gnomad MID AF: 0.554

Gnomad NFE AF: 0.681

Gnomad OTH AF: 0.577

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

GnomAD4 genome AF: 0.537 AC: 81713 AN: 152098 Hom.: 25232 Cov.: 32 AF XY: 0.540 AC XY: 40151 AN XY: 74344

Gnomad4 AFR AF: 0.209

Gnomad4 AMR AF: 0.654

Gnomad4 ASJ AF: 0.646

Gnomad4 EAS AF: 0.531

Gnomad4 SAS AF: 0.656

Gnomad4 FIN AF: 0.617

Gnomad4 NFE AF: 0.681

Gnomad4 OTH AF: 0.575

Alfa AF: 0.581 Hom.: 3470

Bravo AF: 0.524

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.88
Cadd	Benign	0.95
Dann	Benign	0.71

Splicing

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

Publications

LitVar

Other links and lift over

dbSNP: rs10956372; hg19: chr8-128470256;