chr8-127323428-G-A

Position:

• chr8-127323428-G-A

Variant summary

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

The ENST00000645438.1(POU5F1B):​c.-715+1202G>A variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.366 in 152,184 control chromosomes in the GnomAD database, including 10,372 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 0.37 (10372 hom., cov: 34)
• Consequence: POU5F1B ENST00000645438.1 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.917

Genes affected

CASC8 (HGNC:):

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=-0.96).
• BA1: GnomAd4 highest subpopulation (SAS) allele frequency at 95% confidence interval = 0.488 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
CASC21	NR_117099.1	n.302+1202G>A		intron_variant
CASC8	NR_117100.1	n.1177-33368C>T		intron_variant

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
CASC8	ENST00000501396.5	n.547-274C>T		intron_variant		1
CASC8	ENST00000502082.5	n.1177-33368C>T		intron_variant		1
CASC8	ENST00000523825.2	n.547-33368C>T		intron_variant		1

Frequencies

GnomAD3 genomes AF: 0.366 AC: 55644 AN: 152068 Hom.: 10352 Cov.: 34

Gnomad AFR AF: 0.346

Gnomad AMI AF: 0.602

Gnomad AMR AF: 0.354

Gnomad ASJ AF: 0.391

Gnomad EAS AF: 0.438

Gnomad SAS AF: 0.506

Gnomad FIN AF: 0.340

Gnomad MID AF: 0.415

Gnomad NFE AF: 0.364

Gnomad OTH AF: 0.381

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

GnomAD4 genome AF: 0.366 AC: 55702 AN: 152184 Hom.: 10372 Cov.: 34 AF XY: 0.368 AC XY: 27394 AN XY: 74386

Gnomad4 AFR AF: 0.346

Gnomad4 AMR AF: 0.354

Gnomad4 ASJ AF: 0.391

Gnomad4 EAS AF: 0.438

Gnomad4 SAS AF: 0.505

Gnomad4 FIN AF: 0.340

Gnomad4 NFE AF: 0.364

Gnomad4 OTH AF: 0.386

Alfa AF: 0.370 Hom.: 6559

Bravo AF: 0.366

Asia WGS AF: 0.480 AC: 1669 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.96
CADD	Benign	1.6
DANN	Benign	0.74

Splicing

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

Publications

LitVar

Other links and lift over

dbSNP: rs620861; hg19: chr8-128335673;