rs11965454

Variant names:

• chr6-31166814-T-C
• rs11965454
• ENST00000606567.6:c.-386A>G

Variant summary

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

The ENST00000606567.6(POU5F1):​c.-386A>G variant causes a 5 prime UTR premature start codon gain change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0393 in 1,187,126 control chromosomes in the GnomAD database, including 1,760 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 0.073 (678 hom., cov: 32)
  • Exomes 𝑓: 0.034 (1082 hom.)
• Consequence: POU5F1 ENST00000606567.6 5_prime_UTR_premature_start_codon_gain
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 0.253
• Publications: 2 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]

TCF19 (HGNC:11629): (transcription factor 19) This gene encodes a protein that contains a PHD-type zinc finger domain and likely functions as a transcription factor. The encoded protein plays a role proliferation and apoptosis of pancreatic beta cells. Alternative splicing results in multiple transcript variants. [provided by RefSeq, Jan 2016]

ACMG classification

Our verdict: Benign. The variant received -12 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.91).
• BA1: GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.158 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
POU5F1	NM_002701.6	c.406-767A>G		intron_variant	Intron 1 of 4	ENST00000259915.13	NP_002692.2

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
POU5F1	ENST00000259915.13	c.406-767A>G		intron_variant	Intron 1 of 4	1	NM_002701.6	ENSP00000259915.7

Frequencies

GnomAD3 genomes AF: 0.0731 AC: 11121 AN: 152094 Hom.: 676 Cov.: 32

Gnomad AFR AF: 0.158

Gnomad AMI AF: 0.0241

Gnomad AMR AF: 0.0416

Gnomad ASJ AF: 0.0444

Gnomad EAS AF: 0.168

Gnomad SAS AF: 0.0427

Gnomad FIN AF: 0.0526

Gnomad MID AF: 0.0443

Gnomad NFE AF: 0.0287

Gnomad OTH AF: 0.0746

GnomAD4 exome AF: 0.0343 AC: 35548 AN: 1034914 Hom.: 1082 Cov.: 31 AF XY: 0.0340 AC XY: 16666 AN XY: 489460

African (AFR) AF: 0.162 AC: 3498 AN: 21638

American (AMR) AF: 0.0366 AC: 295 AN: 8060

Ashkenazi Jewish (ASJ) AF: 0.0487 AC: 632 AN: 12978

East Asian (EAS) AF: 0.177 AC: 3318 AN: 18694

South Asian (SAS) AF: 0.0350 AC: 1462 AN: 41820

European-Finnish (FIN) AF: 0.0590 AC: 348 AN: 5898

Middle Eastern (MID) AF: 0.0387 AC: 99 AN: 2560

European-Non Finnish (NFE) AF: 0.0270 AC: 23870 AN: 883188

Other (OTH) AF: 0.0506 AC: 2026 AN: 40078

GnomAD4 genome AF: 0.0731 AC: 11131 AN: 152212 Hom.: 678 Cov.: 32 AF XY: 0.0740 AC XY: 5508 AN XY: 74420

African (AFR) AF: 0.158 AC: 6562 AN: 41492

American (AMR) AF: 0.0415 AC: 635 AN: 15302

Ashkenazi Jewish (ASJ) AF: 0.0444 AC: 154 AN: 3472

East Asian (EAS) AF: 0.167 AC: 867 AN: 5186

South Asian (SAS) AF: 0.0427 AC: 206 AN: 4820

European-Finnish (FIN) AF: 0.0526 AC: 558 AN: 10604

Middle Eastern (MID) AF: 0.0476 AC: 14 AN: 294

European-Non Finnish (NFE) AF: 0.0287 AC: 1954 AN: 68018

Other (OTH) AF: 0.0753 AC: 159 AN: 2112

Alfa AF: 0.0522 Hom.: 619

Bravo AF: 0.0784

Asia WGS AF: 0.115 AC: 400 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	5.3
DANN	Benign	0.76
PhyloP100		0.25
PromoterAI		0.0030	Neutral
Mutation Taster		=100/0	polymorphism (auto)

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

Other links and lift over

dbSNP: rs11965454; hg19: chr6-31134591;