chr6-31172443-T-C

Variant names:

• chr6-31172443-T-C
• rs885949
• ENST00000441888.7:c.-183-6396A>G

Variant summary

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

The ENST00000441888.7(POU5F1):​c.-183-6396A>G variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.177 in 152,212 control chromosomes in the GnomAD database, including 2,605 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 0.18 (2605 hom., cov: 32)
• Consequence: POU5F1 ENST00000441888.7 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -1.83
• Publications: 8 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=-0.66).
• BA1: GnomAd4 highest subpopulation (SAS) allele frequency at 95% confidence interval = 0.266 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.-183-6396A>G		intron_variant	Intron 1 of 4	1		ENSP00000389359.2

Frequencies

GnomAD3 genomes AF: 0.177 AC: 26955 AN: 152094 Hom.: 2599 Cov.: 32

Gnomad AFR AF: 0.147

Gnomad AMI AF: 0.196

Gnomad AMR AF: 0.191

Gnomad ASJ AF: 0.238

Gnomad EAS AF: 0.195

Gnomad SAS AF: 0.277

Gnomad FIN AF: 0.295

Gnomad MID AF: 0.278

Gnomad NFE AF: 0.161

Gnomad OTH AF: 0.198

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

GnomAD4 genome AF: 0.177 AC: 26986 AN: 152212 Hom.: 2605 Cov.: 32 AF XY: 0.185 AC XY: 13802 AN XY: 74414

African (AFR) AF: 0.147 AC: 6098 AN: 41538

American (AMR) AF: 0.191 AC: 2926 AN: 15294

Ashkenazi Jewish (ASJ) AF: 0.238 AC: 825 AN: 3472

East Asian (EAS) AF: 0.195 AC: 1010 AN: 5178

South Asian (SAS) AF: 0.278 AC: 1344 AN: 4828

European-Finnish (FIN) AF: 0.295 AC: 3129 AN: 10592

Middle Eastern (MID) AF: 0.289 AC: 85 AN: 294

European-Non Finnish (NFE) AF: 0.161 AC: 10973 AN: 68002

Other (OTH) AF: 0.198 AC: 418 AN: 2108

Alfa AF: 0.167 Hom.: 4558

Bravo AF: 0.168

Asia WGS AF: 0.221 AC: 771 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.66
CADD	Benign	2.6
DANN	Benign	0.85
PhyloP100		-1.8
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: rs885949; hg19: chr6-31140220;