rs3130504

chr6-31170060-A-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+156T>A variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.753 in 1,209,756 control chromosomes in the GnomAD database, including 344,630 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 0.78 (46572 hom., cov: 32)
  • Exomes 𝑓: 0.75 (298058 hom.)
• Consequence: POU5F1 NM_002701.6 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -3.90

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=-0.91).
• BA1: GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.84 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
POU5F1	NM_002701.6	c.405+156T>A		intron_variant		ENST00000259915.13

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
POU5F1	ENST00000259915.13	c.405+156T>A		intron_variant		1	NM_002701.6	P1
POU5F1	ENST00000441888.7	c.-183-4013T>A		intron_variant		1
POU5F1	ENST00000461401.1	n.443+156T>A		intron_variant, non_coding_transcript_variant		1

Frequencies

GnomAD3 genomes AF: 0.781 AC: 118618 AN: 151940 Hom.: 46533 Cov.: 32

Gnomad AFR AF: 0.847

Gnomad AMI AF: 0.805

Gnomad AMR AF: 0.805

Gnomad ASJ AF: 0.862

Gnomad EAS AF: 0.679

Gnomad SAS AF: 0.687

Gnomad FIN AF: 0.749

Gnomad MID AF: 0.889

Gnomad NFE AF: 0.748

Gnomad OTH AF: 0.818

GnomAD4 exome AF: 0.749 AC: 792336 AN: 1057698 Hom.: 298058 Cov.: 14 AF XY: 0.748 AC XY: 395521 AN XY: 528782

Gnomad4 AFR exome AF: 0.852

Gnomad4 AMR exome AF: 0.780

Gnomad4 ASJ exome AF: 0.856

Gnomad4 EAS exome AF: 0.641

Gnomad4 SAS exome AF: 0.715

Gnomad4 FIN exome AF: 0.742

Gnomad4 NFE exome AF: 0.749

Gnomad4 OTH exome AF: 0.765

GnomAD4 genome AF: 0.781 AC: 118711 AN: 152058 Hom.: 46572 Cov.: 32 AF XY: 0.780 AC XY: 57919 AN XY: 74278

Gnomad4 AFR AF: 0.847

Gnomad4 AMR AF: 0.805

Gnomad4 ASJ AF: 0.862

Gnomad4 EAS AF: 0.679

Gnomad4 SAS AF: 0.686

Gnomad4 FIN AF: 0.749

Gnomad4 NFE AF: 0.748

Gnomad4 OTH AF: 0.817

Alfa AF: 0.761 Hom.: 5497

Bravo AF: 0.790

Asia WGS AF: 0.756 AC: 2630 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.91
Cadd	Benign	0.16
Dann	Benign	0.57
RBP_binding_hub_radar		0.0
RBP_regulation_power_radar		1.2

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: rs3130504; hg19: chr6-31137837;