rs6994721

Positions:

• chr8-75145478-A-G
• chr8-75145478-A-T

Variant summary

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

The ENST00000676364.1(CASC9):​n.251-23722T>C variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.486 in 151,766 control chromosomes in the GnomAD database, including 18,776 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 0.49 (18776 hom., cov: 32)
• Consequence: CASC9 ENST00000676364.1 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -1.18

Genes affected

CASC9 (HGNC:48906): (cancer susceptibility 9)

ACMG classification

Verdict is Benign. Variant got -12 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.99).
• BA1: GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.645 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
CASC9	ENST00000676364.1	n.251-23722T>C		intron_variant

Frequencies

GnomAD3 genomes AF: 0.486 AC: 73677 AN: 151646 Hom.: 18750 Cov.: 32

Gnomad AFR AF: 0.651

Gnomad AMI AF: 0.479

Gnomad AMR AF: 0.496

Gnomad ASJ AF: 0.364

Gnomad EAS AF: 0.339

Gnomad SAS AF: 0.382

Gnomad FIN AF: 0.483

Gnomad MID AF: 0.391

Gnomad NFE AF: 0.409

Gnomad OTH AF: 0.469

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

GnomAD4 genome AF: 0.486 AC: 73752 AN: 151766 Hom.: 18776 Cov.: 32 AF XY: 0.486 AC XY: 36011 AN XY: 74130

Gnomad4 AFR AF: 0.651

Gnomad4 AMR AF: 0.496

Gnomad4 ASJ AF: 0.364

Gnomad4 EAS AF: 0.338

Gnomad4 SAS AF: 0.380

Gnomad4 FIN AF: 0.483

Gnomad4 NFE AF: 0.409

Gnomad4 OTH AF: 0.471

Alfa AF: 0.413 Hom.: 25759

Bravo AF: 0.497

Asia WGS AF: 0.395 AC: 1371 AN: 3468

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.99
CADD	Benign	0.11
DANN	Benign	0.51

Splicing

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

Publications

LitVar

Other links and lift over

dbSNP: rs6994721; hg19: chr8-76057713;