ENST00000441888.7:c.-183-6345G>C

Variant names:

• chr6-31172392-C-G
• rs3132518
• ENST00000441888.7:c.-183-6345G>C

Variant summary

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

The ENST00000441888.7(POU5F1):​c.-183-6345G>C variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.602 in 151,924 control chromosomes in the GnomAD database, including 27,558 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 0.60 (27558 hom., cov: 32)
• Consequence: POU5F1 ENST00000441888.7 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 0.182
• Publications: 4 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=-0.85).
• BA1: GnomAd4 highest subpopulation (SAS) allele frequency at 95% confidence interval = 0.646 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.-183-6345G>C		intron	N/A	ENSP00000389359.2	F2Z381

Frequencies

GnomAD3 genomes AF: 0.602 AC: 91345 AN: 151806 Hom.: 27535 Cov.: 32

Gnomad AFR AF: 0.586

Gnomad AMI AF: 0.643

Gnomad AMR AF: 0.636

Gnomad ASJ AF: 0.608

Gnomad EAS AF: 0.577

Gnomad SAS AF: 0.666

Gnomad FIN AF: 0.657

Gnomad MID AF: 0.725

Gnomad NFE AF: 0.590

Gnomad OTH AF: 0.605

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

GnomAD4 genome AF: 0.602 AC: 91405 AN: 151924 Hom.: 27558 Cov.: 32 AF XY: 0.605 AC XY: 44943 AN XY: 74256

African (AFR) AF: 0.586 AC: 24280 AN: 41418

American (AMR) AF: 0.636 AC: 9727 AN: 15282

Ashkenazi Jewish (ASJ) AF: 0.608 AC: 2107 AN: 3468

East Asian (EAS) AF: 0.578 AC: 2976 AN: 5148

South Asian (SAS) AF: 0.665 AC: 3206 AN: 4818

European-Finnish (FIN) AF: 0.657 AC: 6928 AN: 10542

Middle Eastern (MID) AF: 0.724 AC: 213 AN: 294

European-Non Finnish (NFE) AF: 0.590 AC: 40106 AN: 67932

Other (OTH) AF: 0.605 AC: 1277 AN: 2112

Alfa AF: 0.482 Hom.: 1400

Bravo AF: 0.598

Asia WGS AF: 0.616 AC: 2142 AN: 3476

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.85
CADD	Benign	8.6
DANN	Benign	0.41
PhyloP100		0.18
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: rs3132518; hg19: chr6-31140169;