8-127414148-G-T

Position:

• chr8-127414148-G-T

Variant summary

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

The NM_001395745.1(POU5F1B):​c.-1299G>T variant causes a 5 prime UTR change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.532 in 151,974 control chromosomes in the GnomAD database, including 22,568 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 0.53 (22568 hom., cov: 32)
• Consequence: POU5F1B NM_001395745.1 5_prime_UTR
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -1.15

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=-0.91).
• BA1: GnomAd4 highest subpopulation (AMR) allele frequency at 95% confidence interval = 0.637 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
POU5F1B	NM_001395745.1	c.-1299G>T		5_prime_UTR_variant	1/2		NP_001382674.1
CASC8	NR_117100.1	n.1176+6681C>A		intron_variant

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
CASC8	ENST00000501396.5	n.546+6681C>A		intron_variant		1
CASC8	ENST00000502082.5	n.1176+6681C>A		intron_variant		1
CASC8	ENST00000523825.2	n.546+6681C>A		intron_variant		1

Frequencies

GnomAD3 genomes AF: 0.532 AC: 80764 AN: 151856 Hom.: 22567 Cov.: 32

Gnomad AFR AF: 0.350

Gnomad AMI AF: 0.475

Gnomad AMR AF: 0.648

Gnomad ASJ AF: 0.587

Gnomad EAS AF: 0.646

Gnomad SAS AF: 0.611

Gnomad FIN AF: 0.575

Gnomad MID AF: 0.598

Gnomad NFE AF: 0.592

Gnomad OTH AF: 0.576

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

GnomAD4 genome AF: 0.532 AC: 80782 AN: 151974 Hom.: 22568 Cov.: 32 AF XY: 0.536 AC XY: 39821 AN XY: 74278

Gnomad4 AFR AF: 0.349

Gnomad4 AMR AF: 0.648

Gnomad4 ASJ AF: 0.587

Gnomad4 EAS AF: 0.646

Gnomad4 SAS AF: 0.611

Gnomad4 FIN AF: 0.575

Gnomad4 NFE AF: 0.592

Gnomad4 OTH AF: 0.579

Alfa AF: 0.535 Hom.: 5747

Bravo AF: 0.529

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.91
CADD	Benign	0.15
DANN	Benign	0.71

Splicing

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

Publications

LitVar

Other links and lift over

dbSNP: rs871135; hg19: chr8-128426393;