chr6-31171140-G-A

Variant names:

• chr6-31171140-G-A
• rs9263817
• ENST00000441888.7:c.-183-5093C>T

Variant summary

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

The ENST00000441888.7(POU5F1):​c.-183-5093C>T variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.151 in 151,776 control chromosomes in the GnomAD database, including 1,882 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 0.15 (1882 hom., cov: 31)
• Consequence: POU5F1 ENST00000441888.7 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.152
• Publications: 3 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=-0.91).
• BA1: GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.175 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.-183-5093C>T		intron_variant	Intron 1 of 4	1		ENSP00000389359.2

Frequencies

GnomAD3 genomes AF: 0.151 AC: 22949 AN: 151660 Hom.: 1874 Cov.: 31

Gnomad AFR AF: 0.177

Gnomad AMI AF: 0.134

Gnomad AMR AF: 0.138

Gnomad ASJ AF: 0.0924

Gnomad EAS AF: 0.0724

Gnomad SAS AF: 0.0665

Gnomad FIN AF: 0.115

Gnomad MID AF: 0.117

Gnomad NFE AF: 0.159

Gnomad OTH AF: 0.167

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

GnomAD4 genome AF: 0.151 AC: 22993 AN: 151776 Hom.: 1882 Cov.: 31 AF XY: 0.148 AC XY: 10965 AN XY: 74130

African (AFR) AF: 0.178 AC: 7355 AN: 41326

American (AMR) AF: 0.138 AC: 2104 AN: 15250

Ashkenazi Jewish (ASJ) AF: 0.0924 AC: 320 AN: 3464

East Asian (EAS) AF: 0.0726 AC: 375 AN: 5166

South Asian (SAS) AF: 0.0678 AC: 326 AN: 4810

European-Finnish (FIN) AF: 0.115 AC: 1212 AN: 10524

Middle Eastern (MID) AF: 0.119 AC: 35 AN: 294

European-Non Finnish (NFE) AF: 0.159 AC: 10798 AN: 67928

Other (OTH) AF: 0.165 AC: 346 AN: 2102

Alfa AF: 0.148 Hom.: 217

Bravo AF: 0.154

Asia WGS AF: 0.102 AC: 356 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.91
CADD	Benign	3.8
DANN	Benign	0.71
PhyloP100		-0.15
PromoterAI		0.015	Neutral
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: rs9263817; hg19: chr6-31138917;