rs1061118

Positions:

• chr6-31164637-G-A

Variant summary

Our verdict is Benign. Variant got -13 ACMG points: 0P and 13B. BP4_Strong BP7 BA1

The NM_002701.6(POU5F1):​c.1047C>T​(p.Ser349=) variant causes a synonymous change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.667 in 1,581,374 control chromosomes in the GnomAD database, including 353,998 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 0.69 (36738 hom., cov: 31)
  • Exomes 𝑓: 0.66 (317260 hom.)
• Consequence: POU5F1 NM_002701.6 synonymous
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 0.00800

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

Verdict is Benign. Variant got -13 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.57).
• BP7: Synonymous conserved (PhyloP=0.008 with no splicing effect.
• BA1: GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.785 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
POU5F1	NM_002701.6	c.1047C>T	p.Ser349=	synonymous_variant	5/5	ENST00000259915.13
POU5F1	NM_001173531.3	c.537C>T	p.Ser179=	synonymous_variant	5/5
POU5F1	NM_203289.6	c.537C>T	p.Ser179=	synonymous_variant	4/4
POU5F1	NM_001285986.2	c.459C>T	p.Ser153=	synonymous_variant	3/3

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
POU5F1	ENST00000259915.13	c.1047C>T	p.Ser349=	synonymous_variant	5/5	1	NM_002701.6	P1

Frequencies

GnomAD3 genomes AF: 0.691 AC: 104888 AN: 151832 Hom.: 36709 Cov.: 31

Gnomad AFR AF: 0.792

Gnomad AMI AF: 0.634

Gnomad AMR AF: 0.680

Gnomad ASJ AF: 0.727

Gnomad EAS AF: 0.634

Gnomad SAS AF: 0.569

Gnomad FIN AF: 0.569

Gnomad MID AF: 0.699

Gnomad NFE AF: 0.663

Gnomad OTH AF: 0.695

GnomAD3 exomes AF: 0.636 AC: 114474 AN: 180008 Hom.: 36722 AF XY: 0.633 AC XY: 61221 AN XY: 96642

Gnomad AFR exome AF: 0.786

Gnomad AMR exome AF: 0.600

Gnomad ASJ exome AF: 0.718

Gnomad EAS exome AF: 0.648

Gnomad SAS exome AF: 0.571

Gnomad FIN exome AF: 0.571

Gnomad NFE exome AF: 0.653

Gnomad OTH exome AF: 0.672

GnomAD4 exome AF: 0.664 AC: 949796 AN: 1429426 Hom.: 317260 Cov.: 52 AF XY: 0.661 AC XY: 468185 AN XY: 707962

Gnomad4 AFR exome AF: 0.796

Gnomad4 AMR exome AF: 0.608

Gnomad4 ASJ exome AF: 0.718

Gnomad4 EAS exome AF: 0.598

Gnomad4 SAS exome AF: 0.581

Gnomad4 FIN exome AF: 0.576

Gnomad4 NFE exome AF: 0.673

Gnomad4 OTH exome AF: 0.675

GnomAD4 genome AF: 0.691 AC: 104965 AN: 151948 Hom.: 36738 Cov.: 31 AF XY: 0.685 AC XY: 50837 AN XY: 74256

Gnomad4 AFR AF: 0.792

Gnomad4 AMR AF: 0.679

Gnomad4 ASJ AF: 0.727

Gnomad4 EAS AF: 0.634

Gnomad4 SAS AF: 0.568

Gnomad4 FIN AF: 0.569

Gnomad4 NFE AF: 0.662

Gnomad4 OTH AF: 0.693

Alfa AF: 0.677 Hom.: 6357

Bravo AF: 0.705

Asia WGS AF: 0.664 AC: 2308 AN: 3476

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.57
CADD	Benign	1.7
DANN	Benign	0.81

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: rs1061118; hg19: chr6-31132414; COSMIC: COSV52564205; COSMIC: COSV52564205;