8-127419449-A-G

Variant names:

• chr8-127419449-A-G
• rs7842552
• ENST00000501396.6:n.546+1380T>C

Variant summary

Our verdict is Benign. The variant received -12 ACMG points: 0P and 12B. BP4_Strong BA1

The ENST00000501396.6(CASC8):​n.546+1380T>C variant causes a intron 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 ENST00000501396.6 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.141
• Publications: 8 publications found

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

Our verdict: Benign. The variant received -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.

Variant Effect in Transcripts

ACMG analysis was done for transcript: ENST00000501396.6. You can select a different transcript below to see updated ACMG assignments.

RefSeq Transcripts

Selected	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	CASC8	NR_117100.1		n.1176+1380T>C		intron	N/A

Ensembl Transcripts

Selected	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	CASC8	ENST00000501396.6	TSL:1	n.546+1380T>C		intron	N/A
	CASC8	ENST00000502082.5	TSL:1	n.1176+1380T>C		intron	N/A
	CASC8	ENST00000523825.3	TSL:1	n.546+1380T>C		intron	N/A

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

African (AFR) AC: 0 AN: 0

American (AMR) AC: 0 AN: 0

Ashkenazi Jewish (ASJ) AC: 0 AN: 0

East Asian (EAS) AC: 0 AN: 0

South Asian (SAS) AC: 0 AN: 0

European-Finnish (FIN) AC: 0 AN: 0

Middle Eastern (MID) AC: 0 AN: 0

European-Non Finnish (NFE) AF: 0.500 AC: 3 AN: 6

Other (OTH) AF: 1.00 AC: 4 AN: 4

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

African (AFR) AF: 0.388 AC: 16065 AN: 41426

American (AMR) AF: 0.210 AC: 3204 AN: 15288

Ashkenazi Jewish (ASJ) AF: 0.281 AC: 973 AN: 3464

East Asian (EAS) AF: 0.205 AC: 1058 AN: 5166

South Asian (SAS) AF: 0.194 AC: 932 AN: 4814

European-Finnish (FIN) AF: 0.326 AC: 3451 AN: 10574

Middle Eastern (MID) AF: 0.337 AC: 99 AN: 294

European-Non Finnish (NFE) AF: 0.288 AC: 19586 AN: 67952

Other (OTH) AF: 0.294 AC: 620 AN: 2110

Alfa AF: 0.287 Hom.: 10594

Bravo AF: 0.301

Asia WGS AF: 0.217 AC: 754 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.90
CADD	Benign	3.3
DANN	Benign	0.49
PhyloP100		-0.14
Mutation Taster		=100/0	polymorphism (auto)

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

Other links and lift over

dbSNP: rs7842552; hg19: chr8-128431694;