rs6910473

Variant names:

• chr6-31173031-G-A
• rs6910473
• ENST00000441888.7:c.-183-6984C>T

Variant summary

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

The ENST00000441888.7(POU5F1):​c.-183-6984C>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
• 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=-0.77).
• BA1: GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.147 is higher than 0.05.

Variant Effect in Transcripts

ACMG analysis was done for transcript: ENST00000441888.7. You can select a different transcript below to see updated ACMG assignments.

RefSeq Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
There are no transcript annotations for this variant.

Ensembl Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	POU5F1	ENST00000441888.7	TSL:1	c.-183-6984C>T		intron	N/A	ENSP00000389359.2	F2Z381

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

African (AFR) AF: 0.150 AC: 6215 AN: 41472

American (AMR) AF: 0.114 AC: 1737 AN: 15266

Ashkenazi Jewish (ASJ) AF: 0.0833 AC: 289 AN: 3470

East Asian (EAS) AF: 0.0721 AC: 373 AN: 5174

South Asian (SAS) AF: 0.0585 AC: 282 AN: 4820

European-Finnish (FIN) AF: 0.0541 AC: 574 AN: 10608

Middle Eastern (MID) AF: 0.0918 AC: 27 AN: 294

European-Non Finnish (NFE) AF: 0.129 AC: 8780 AN: 68006

Other (OTH) AF: 0.134 AC: 283 AN: 2108

Alfa AF: 0.128 Hom.: 374

Bravo AF: 0.128

Asia WGS AF: 0.0770 AC: 270 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.77
CADD	Benign	15
DANN	Benign	0.88
PhyloP100		1.0
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: rs6910473; hg19: chr6-31140808;