chr6-31172838-C-T

Variant names:

• chr6-31172838-C-T
• rs9501065
• ENST00000441888.7:c.-183-6791G>A

Variant summary

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

The ENST00000441888.7(POU5F1):​c.-183-6791G>A variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.129 in 152,116 control chromosomes in the GnomAD database, including 1,591 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 0.13 (1591 hom., cov: 31)
• Consequence: POU5F1 ENST00000441888.7 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.310
• Publications: 2 publications found

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

Our verdict: Benign. The variant received -12 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.86).
• BA1: GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.204 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
POU5F1	ENST00000441888.7	c.-183-6791G>A		intron_variant	Intron 1 of 4	1		ENSP00000389359.2

Frequencies

GnomAD3 genomes AF: 0.129 AC: 19673 AN: 151998 Hom.: 1588 Cov.: 31

Gnomad AFR AF: 0.208

Gnomad AMI AF: 0.0526

Gnomad AMR AF: 0.109

Gnomad ASJ AF: 0.261

Gnomad EAS AF: 0.197

Gnomad SAS AF: 0.200

Gnomad FIN AF: 0.0930

Gnomad MID AF: 0.136

Gnomad NFE AF: 0.0759

Gnomad OTH AF: 0.142

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

GnomAD4 genome AF: 0.129 AC: 19685 AN: 152116 Hom.: 1591 Cov.: 31 AF XY: 0.132 AC XY: 9815 AN XY: 74348

African (AFR) AF: 0.207 AC: 8602 AN: 41466

American (AMR) AF: 0.109 AC: 1665 AN: 15282

Ashkenazi Jewish (ASJ) AF: 0.261 AC: 905 AN: 3470

East Asian (EAS) AF: 0.197 AC: 1017 AN: 5168

South Asian (SAS) AF: 0.199 AC: 959 AN: 4816

European-Finnish (FIN) AF: 0.0930 AC: 984 AN: 10584

Middle Eastern (MID) AF: 0.136 AC: 40 AN: 294

European-Non Finnish (NFE) AF: 0.0759 AC: 5164 AN: 68018

Other (OTH) AF: 0.143 AC: 301 AN: 2106

Alfa AF: 0.0634 Hom.: 111

Bravo AF: 0.135

Asia WGS AF: 0.215 AC: 746 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.86
CADD	Benign	2.8
DANN	Benign	0.70
PhyloP100		-0.31
Mutation Taster		=100/0	polymorphism (auto)

Splicing

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

Other links and lift over

dbSNP: rs9501065; hg19: chr6-31140615;