rs3734864

Positions:

• chr6-31164526-C-T

Variant summary

Our verdict is Benign. Variant got -12 ACMG points: 0P and 12B. BP4_Strong BS1 BS2

The NM_002701.6(POU5F1):​c.*75G>A variant causes a 3 prime UTR change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00172 in 1,561,420 control chromosomes in the GnomAD database, including 74 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 0.0014 (2 hom., cov: 32)
  • Exomes 𝑓: 0.0018 (72 hom.)
• Consequence: POU5F1 NM_002701.6 3_prime_UTR
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 0.297

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 -12 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.57).
• BS1: Variant frequency is greater than expected in population eas. gnomad4_exome allele frequency = 0.00175 (2472/1409108) while in subpopulation EAS AF= 0.047 (1752/37282). AF 95% confidence interval is 0.0452. There are 72 homozygotes in gnomad4_exome. There are 1203 alleles in male gnomad4_exome subpopulation. Median coverage is 31. This position pass quality control queck.
• BS2: High AC in GnomAd4 at 215 AD gene.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
POU5F1	NM_002701.6	c.*75G>A		3_prime_UTR_variant	5/5	ENST00000259915.13	NP_002692.2
POU5F1	NM_001173531.3	c.*75G>A		3_prime_UTR_variant	5/5		NP_001167002.1
POU5F1	NM_001285986.2	c.*75G>A		3_prime_UTR_variant	3/3		NP_001272915.1
POU5F1	NM_203289.6	c.*75G>A		3_prime_UTR_variant	4/4		NP_976034.4

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
POU5F1	ENST00000259915.13	c.*75G>A		3_prime_UTR_variant	5/5	1	NM_002701.6	ENSP00000259915	P1

Frequencies

GnomAD3 genomes AF: 0.00140 AC: 213 AN: 152194 Hom.: 2 Cov.: 32

Gnomad AFR AF: 0.00229

Gnomad AMI AF: 0.00

Gnomad AMR AF: 0.000654

Gnomad ASJ AF: 0.000865

Gnomad EAS AF: 0.0131

Gnomad SAS AF: 0.000414

Gnomad FIN AF: 0.0000942

Gnomad MID AF: 0.00

Gnomad NFE AF: 0.000382

Gnomad OTH AF: 0.00382

GnomAD4 exome AF: 0.00175 AC: 2472 AN: 1409108 Hom.: 72 Cov.: 31 AF XY: 0.00173 AC XY: 1203 AN XY: 696492

Gnomad4 AFR exome AF: 0.00280

Gnomad4 AMR exome AF: 0.00121

Gnomad4 ASJ exome AF: 0.00111

Gnomad4 EAS exome AF: 0.0470

Gnomad4 SAS exome AF: 0.000237

Gnomad4 FIN exome AF: 0.0000597

Gnomad4 NFE exome AF: 0.000434

Gnomad4 OTH exome AF: 0.00101

GnomAD4 genome AF: 0.00141 AC: 215 AN: 152312 Hom.: 2 Cov.: 32 AF XY: 0.00134 AC XY: 100 AN XY: 74484

Gnomad4 AFR AF: 0.00236

Gnomad4 AMR AF: 0.000653

Gnomad4 ASJ AF: 0.000865

Gnomad4 EAS AF: 0.0131

Gnomad4 SAS AF: 0.000207

Gnomad4 FIN AF: 0.0000942

Gnomad4 NFE AF: 0.000382

Gnomad4 OTH AF: 0.00378

Alfa AF: 0.00103 Hom.: 0

Bravo AF: 0.00157

Asia WGS AF: 0.00779 AC: 27 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.57
CADD	Benign	9.0
DANN	Benign	0.63

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: rs3734864; hg19: chr6-31132303;