6-31170695-C-T

Position:

• chr6-31170695-C-T

Variant summary

Our verdict is Benign. Variant got -10 ACMG points: 0P and 10B. BP4_Moderate BA1

The ENST00000441888.7(POU5F1):​c.-183-4648G>A variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0405 in 1,466,142 control chromosomes in the GnomAD database, including 2,348 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 0.072 (667 hom., cov: 32)
  • Exomes 𝑓: 0.037 (1681 hom.)
• Consequence: POU5F1 ENST00000441888.7 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 1.65

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

Verdict is Benign. Variant got -10 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.37).
• BA1: GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.157 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
POU5F1	NM_002701.6			upstream_gene_variant		ENST00000259915.13	NP_002692.2

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
POU5F1	ENST00000441888.7	c.-183-4648G>A		intron_variant		1		ENSP00000389359
POU5F1	ENST00000259915.13			upstream_gene_variant		1	NM_002701.6	ENSP00000259915	P1
POU5F1	ENST00000461401.1			upstream_gene_variant		1

Frequencies

GnomAD3 genomes AF: 0.0721 AC: 10964 AN: 152084 Hom.: 665 Cov.: 32

Gnomad AFR AF: 0.158

Gnomad AMI AF: 0.0242

Gnomad AMR AF: 0.0404

Gnomad ASJ AF: 0.0196

Gnomad EAS AF: 0.167

Gnomad SAS AF: 0.0415

Gnomad FIN AF: 0.0528

Gnomad MID AF: 0.0443

Gnomad NFE AF: 0.0283

Gnomad OTH AF: 0.0709

GnomAD4 exome AF: 0.0368 AC: 48416 AN: 1313938 Hom.: 1681 Cov.: 32 AF XY: 0.0365 AC XY: 23332 AN XY: 638742

Gnomad4 AFR exome AF: 0.163

Gnomad4 AMR exome AF: 0.0334

Gnomad4 ASJ exome AF: 0.0225

Gnomad4 EAS exome AF: 0.183

Gnomad4 SAS exome AF: 0.0367

Gnomad4 FIN exome AF: 0.0584

Gnomad4 NFE exome AF: 0.0271

Gnomad4 OTH exome AF: 0.0503

GnomAD4 genome AF: 0.0721 AC: 10975 AN: 152204 Hom.: 667 Cov.: 32 AF XY: 0.0728 AC XY: 5422 AN XY: 74434

Gnomad4 AFR AF: 0.158

Gnomad4 AMR AF: 0.0403

Gnomad4 ASJ AF: 0.0196

Gnomad4 EAS AF: 0.166

Gnomad4 SAS AF: 0.0415

Gnomad4 FIN AF: 0.0528

Gnomad4 NFE AF: 0.0283

Gnomad4 OTH AF: 0.0716

Alfa AF: 0.0626 Hom.: 74

Bravo AF: 0.0775

Asia WGS AF: 0.115 AC: 398 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.37
CADD	Benign	20
DANN	Benign	0.89

Splicing

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

Publications

LitVar

Other links and lift over

dbSNP: rs17197199; hg19: chr6-31138472;