rs924993

Positions:

• chr8-127292254-G-A

Variant summary

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

The ENST00000605028.1(ENSG00000271509):​n.22G>A variant causes a non coding transcript exon change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0507 in 152,166 control chromosomes in the GnomAD database, including 447 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 0.051 (447 hom., cov: 32)
  • Exomes 𝑓: 0.17 (0 hom.)
• Consequence: ENSG00000271509 ENST00000605028.1 non_coding_transcript_exon
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.00700

Genes affected

CASC8 (HGNC:):

ACMG classification

Verdict is Benign. Variant got -12 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.91).
• BA1: GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.271 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
CASC21	NR_117099.1	n.149-29819G>A		intron_variant
CASC8	NR_117100.1	n.1177-2194C>T		intron_variant

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
CASC8	ENST00000501396.5	n.687-2194C>T		intron_variant		1
CASC8	ENST00000502082.5	n.1177-2194C>T		intron_variant		1
CASC8	ENST00000523825.2	n.547-2194C>T		intron_variant		1

Frequencies

GnomAD3 genomes AF: 0.0506 AC: 7692 AN: 152042 Hom.: 442 Cov.: 32

Gnomad AFR AF: 0.0548

Gnomad AMI AF: 0.0714

Gnomad AMR AF: 0.117

Gnomad ASJ AF: 0.0338

Gnomad EAS AF: 0.283

Gnomad SAS AF: 0.0964

Gnomad FIN AF: 0.0440

Gnomad MID AF: 0.0380

Gnomad NFE AF: 0.0136

Gnomad OTH AF: 0.0583

GnomAD4 exome AF: 0.167 AC: 1 AN: 6 Hom.: 0 Cov.: 0 AF XY: 0.00 AC XY: 0 AN XY: 4

Gnomad4 NFE exome AF: 0.167

GnomAD4 genome AF: 0.0507 AC: 7712 AN: 152160 Hom.: 447 Cov.: 32 AF XY: 0.0561 AC XY: 4173 AN XY: 74378

Gnomad4 AFR AF: 0.0547

Gnomad4 AMR AF: 0.118

Gnomad4 ASJ AF: 0.0338

Gnomad4 EAS AF: 0.283

Gnomad4 SAS AF: 0.0969

Gnomad4 FIN AF: 0.0440

Gnomad4 NFE AF: 0.0136

Gnomad4 OTH AF: 0.0596

Alfa AF: 0.0288 Hom.: 186

Bravo AF: 0.0608

Asia WGS AF: 0.204 AC: 705 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.91
CADD	Benign	2.2
DANN	Benign	0.40

Splicing

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

Publications

LitVar

Other links and lift over

dbSNP: rs924993; hg19: chr8-128304499;