rs6910473

Positions:

• chr6-31173031-G-A

Variant summary

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

The ENST00000441888.7(POU5F1):​c.-183-6984C>T variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.123 in 152,126 control chromosomes in the GnomAD database, including 1,278 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 0.12 (1278 hom., cov: 32)
• Consequence: POU5F1 ENST00000441888.7 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 1.02

Genes affected

POU5F1 (HGNC:9221): (POU class 5 homeobox 1) This gene encodes a transcription factor containing a POU homeodomain that plays a key role in embryonic development and stem cell pluripotency. Aberrant expression of this gene in adult tissues is associated with tumorigenesis. This gene can participate in a translocation with the Ewing's sarcoma gene on chromosome 21, which also leads to tumor formation. Alternative splicing, as well as usage of alternative AUG and non-AUG translation initiation codons, results in multiple isoforms. One of the AUG start codons is polymorphic in human populations. Related pseudogenes have been identified on chromosomes 1, 3, 8, 10, and 12. [provided by RefSeq, Oct 2013]

ACMG classification

Verdict is Benign. Variant got -12 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.77).
• BA1: GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.147 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
POU5F1	ENST00000441888.7	c.-183-6984C>T		intron_variant		1		ENSP00000389359

Frequencies

GnomAD3 genomes AF: 0.123 AC: 18646 AN: 152008 Hom.: 1271 Cov.: 32

Gnomad AFR AF: 0.149

Gnomad AMI AF: 0.133

Gnomad AMR AF: 0.114

Gnomad ASJ AF: 0.0833

Gnomad EAS AF: 0.0719

Gnomad SAS AF: 0.0576

Gnomad FIN AF: 0.0541

Gnomad MID AF: 0.0918

Gnomad NFE AF: 0.129

Gnomad OTH AF: 0.136

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

GnomAD4 genome AF: 0.123 AC: 18681 AN: 152126 Hom.: 1278 Cov.: 32 AF XY: 0.118 AC XY: 8811 AN XY: 74374

Gnomad4 AFR AF: 0.150

Gnomad4 AMR AF: 0.114

Gnomad4 ASJ AF: 0.0833

Gnomad4 EAS AF: 0.0721

Gnomad4 SAS AF: 0.0585

Gnomad4 FIN AF: 0.0541

Gnomad4 NFE AF: 0.129

Gnomad4 OTH AF: 0.134

Alfa AF: 0.127 Hom.: 255

Bravo AF: 0.128

Asia WGS AF: 0.0770 AC: 270 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.77
CADD	Benign	15
DANN	Benign	0.88

Splicing

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

Publications

LitVar

Other links and lift over

dbSNP: rs6910473; hg19: chr6-31140808;