6-31169997-G-T

Position:

• chr6-31169997-G-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+219C>A variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.607 in 700,508 control chromosomes in the GnomAD database, including 130,552 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 0.63 (30426 hom., cov: 31)
  • Exomes 𝑓: 0.60 (100126 hom.)
• Consequence: POU5F1 NM_002701.6 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.00400

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=-0.88).
• BA1: GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.68 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
POU5F1	NM_002701.6	c.405+219C>A		intron_variant		ENST00000259915.13

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
POU5F1	ENST00000259915.13	c.405+219C>A		intron_variant		1	NM_002701.6	P1
POU5F1	ENST00000441888.7	c.-183-3950C>A		intron_variant		1
POU5F1	ENST00000461401.1	n.443+219C>A		intron_variant, non_coding_transcript_variant		1

Frequencies

GnomAD3 genomes AF: 0.631 AC: 95756 AN: 151704 Hom.: 30418 Cov.: 31

Gnomad AFR AF: 0.687

Gnomad AMI AF: 0.670

Gnomad AMR AF: 0.663

Gnomad ASJ AF: 0.766

Gnomad EAS AF: 0.605

Gnomad SAS AF: 0.596

Gnomad FIN AF: 0.633

Gnomad MID AF: 0.747

Gnomad NFE AF: 0.586

Gnomad OTH AF: 0.646

GnomAD4 exome AF: 0.600 AC: 329234 AN: 548688 Hom.: 100126 Cov.: 7 AF XY: 0.600 AC XY: 171075 AN XY: 285104

Gnomad4 AFR exome AF: 0.689

Gnomad4 AMR exome AF: 0.667

Gnomad4 ASJ exome AF: 0.760

Gnomad4 EAS exome AF: 0.601

Gnomad4 SAS exome AF: 0.603

Gnomad4 FIN exome AF: 0.626

Gnomad4 NFE exome AF: 0.582

Gnomad4 OTH exome AF: 0.620

GnomAD4 genome AF: 0.631 AC: 95802 AN: 151820 Hom.: 30426 Cov.: 31 AF XY: 0.632 AC XY: 46901 AN XY: 74162

Gnomad4 AFR AF: 0.687

Gnomad4 AMR AF: 0.663

Gnomad4 ASJ AF: 0.766

Gnomad4 EAS AF: 0.605

Gnomad4 SAS AF: 0.594

Gnomad4 FIN AF: 0.633

Gnomad4 NFE AF: 0.586

Gnomad4 OTH AF: 0.648

Alfa AF: 0.618 Hom.: 7732

Bravo AF: 0.640

Asia WGS AF: 0.643 AC: 2234 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.88
CADD	Benign	3.5
DANN	Benign	0.83

Splicing

Name	Calibrated prediction	Score	Prediction
SpliceAI score (max)		0.10		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: rs3094193; hg19: chr6-31137774;