8-127419449-A-G

Position:

• chr8-127419449-A-G

Variant summary

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

The NR_117100.1(CASC8):​n.1176+1380T>C 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 0.305 in 152,010 control chromosomes in the GnomAD database, including 7,460 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 0.30 (7457 hom., cov: 32)
  • Exomes 𝑓: 0.70 (3 hom.)
• Consequence: CASC8 NR_117100.1 intron, non_coding_transcript
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.141

Genes affected

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

POU5F1B (HGNC:9223): (POU class 5 homeobox 1B) This intronless gene was thought to be a transcribed pseudogene of POU class 5 homeobox 1, however, it has been reported that this gene can encode a functional protein. The encoded protein is nearly the same length as and highly similar to the POU class 5 homeobox 1 transcription factor, has been shown to be a weak transcriptional activator and may play a role in carcinogenesis and eye development. [provided by RefSeq, Apr 2009]

ACMG classification

Verdict is Benign. Variant got -12 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.9).
• BA1: GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.383 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
CASC8	NR_117100.1	n.1176+1380T>C		intron_variant, non_coding_transcript_variant

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
CASC8	ENST00000501396.5	n.546+1380T>C		intron_variant, non_coding_transcript_variant		1
CASC8	ENST00000502082.5	n.1176+1380T>C		intron_variant, non_coding_transcript_variant		1
CASC8	ENST00000523825.2	n.546+1380T>C		intron_variant, non_coding_transcript_variant		1
POU5F1B	ENST00000465342.4	c.*2503A>G		3_prime_UTR_variant	3/3	3		ENSP00000419298	P1

Frequencies

GnomAD3 genomes AF: 0.305 AC: 46312 AN: 151882 Hom.: 7454 Cov.: 32

Gnomad AFR AF: 0.388

Gnomad AMI AF: 0.376

Gnomad AMR AF: 0.210

Gnomad ASJ AF: 0.281

Gnomad EAS AF: 0.204

Gnomad SAS AF: 0.195

Gnomad FIN AF: 0.326

Gnomad MID AF: 0.335

Gnomad NFE AF: 0.288

Gnomad OTH AF: 0.298

GnomAD4 exome AF: 0.700 AC: 7 AN: 10 Hom.: 3 Cov.: 0 AF XY: 0.833 AC XY: 5 AN XY: 6

Gnomad4 NFE exome AF: 0.500

Gnomad4 OTH exome AF: 1.00

GnomAD4 genome AF: 0.305 AC: 46331 AN: 152000 Hom.: 7457 Cov.: 32 AF XY: 0.303 AC XY: 22517 AN XY: 74312

Gnomad4 AFR AF: 0.388

Gnomad4 AMR AF: 0.210

Gnomad4 ASJ AF: 0.281

Gnomad4 EAS AF: 0.205

Gnomad4 SAS AF: 0.194

Gnomad4 FIN AF: 0.326

Gnomad4 NFE AF: 0.288

Gnomad4 OTH AF: 0.294

Alfa AF: 0.284 Hom.: 7201

Bravo AF: 0.301

Asia WGS AF: 0.217 AC: 754 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.90
CADD	Benign	3.3
DANN	Benign	0.49

Splicing

Name	Calibrated prediction	Score	Prediction
SpliceAI score (max)		0.0		Details are displayed if max score is > 0.2

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

Publications

LitVar

Other links and lift over

dbSNP: rs7842552; hg19: chr8-128431694;