6-31169968-C-T

Position:

• chr6-31169968-C-T

Variant summary

Our verdict is Benign. Variant got -12 ACMG points: 0P and 12B. BP4_Strong BA1

The NM_002701.6(POU5F1):​c.405+248G>A variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.139 in 621,108 control chromosomes in the GnomAD database, including 6,722 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 (1734 hom., cov: 32)
  • Exomes 𝑓: 0.14 (4988 hom.)
• Consequence: POU5F1 NM_002701.6 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -1.53

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 -12 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.82).
• BA1: GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.157 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
POU5F1	NM_002701.6	c.405+248G>A		intron_variant		ENST00000259915.13

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
POU5F1	ENST00000259915.13	c.405+248G>A		intron_variant		1	NM_002701.6	P1
POU5F1	ENST00000441888.7	c.-183-3921G>A		intron_variant		1
POU5F1	ENST00000461401.1	n.443+248G>A		intron_variant, non_coding_transcript_variant		1

Frequencies

GnomAD3 genomes AF: 0.146 AC: 22130 AN: 152012 Hom.: 1726 Cov.: 32

Gnomad AFR AF: 0.159

Gnomad AMI AF: 0.134

Gnomad AMR AF: 0.133

Gnomad ASJ AF: 0.0922

Gnomad EAS AF: 0.0725

Gnomad SAS AF: 0.0668

Gnomad FIN AF: 0.115

Gnomad MID AF: 0.117

Gnomad NFE AF: 0.159

Gnomad OTH AF: 0.162

GnomAD4 exome AF: 0.137 AC: 64062 AN: 468978 Hom.: 4988 Cov.: 5 AF XY: 0.134 AC XY: 32738 AN XY: 245054

Gnomad4 AFR exome AF: 0.155

Gnomad4 AMR exome AF: 0.115

Gnomad4 ASJ exome AF: 0.0901

Gnomad4 EAS exome AF: 0.0357

Gnomad4 SAS exome AF: 0.0757

Gnomad4 FIN exome AF: 0.118

Gnomad4 NFE exome AF: 0.161

Gnomad4 OTH exome AF: 0.138

GnomAD4 genome AF: 0.146 AC: 22175 AN: 152130 Hom.: 1734 Cov.: 32 AF XY: 0.143 AC XY: 10606 AN XY: 74362

Gnomad4 AFR AF: 0.160

Gnomad4 AMR AF: 0.133

Gnomad4 ASJ AF: 0.0922

Gnomad4 EAS AF: 0.0727

Gnomad4 SAS AF: 0.0681

Gnomad4 FIN AF: 0.115

Gnomad4 NFE AF: 0.159

Gnomad4 OTH AF: 0.160

Alfa AF: 0.151 Hom.: 208

Bravo AF: 0.147

Asia WGS AF: 0.101 AC: 352 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.82
CADD	Benign	5.0
DANN	Benign	0.72
RBP_binding_hub_radar		0.0
RBP_regulation_power_radar		1.0

Splicing

Name	Calibrated prediction	Score	Prediction
SpliceAI score (max)		0.0		Details are displayed if max score is > 0.2

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

Publications

LitVar

Other links and lift over

dbSNP: rs9263811; hg19: chr6-31137745;