rs9263795

Variant names:

• chr6-31164879-T-C
• rs9263795
• NM_002701.6:c.817-12A>G

Variant summary

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

The NM_002701.6(POU5F1):​c.817-12A>G variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0749 in 1,605,982 control chromosomes in the GnomAD database, including 5,373 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 0.053 (275 hom., cov: 34)
  • Exomes 𝑓: 0.077 (5098 hom.)
• Consequence: POU5F1 NM_002701.6 intron
• Scores: Splicing: ADA: 0.00001850
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.168
• Publications: 5 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=-0.88).
• BA1: GnomAd4 highest subpopulation (NFE) allele frequency at 95% confidence interval = 0.0783 is higher than 0.05.

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_002701.6. You can select a different transcript below to see updated ACMG assignments.

RefSeq Transcripts

Selected	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	POU5F1	NM_002701.6	MANE Select	c.817-12A>G		intron	N/A	NP_002692.2
	POU5F1	NM_001173531.3		c.307-12A>G		intron	N/A	NP_001167002.1
	POU5F1	NM_203289.6		c.307-12A>G		intron	N/A	NP_976034.4

Ensembl Transcripts

Selected	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	POU5F1	ENST00000259915.13	TSL:1 MANE Select	c.817-12A>G		intron	N/A	ENSP00000259915.7
	POU5F1	ENST00000606567.6	TSL:1	c.307-12A>G		intron	N/A	ENSP00000475880.2
	POU5F1	ENST00000441888.7	TSL:1	c.229-12A>G		intron	N/A	ENSP00000389359.2

Frequencies

GnomAD3 genomes AF: 0.0526 AC: 7818 AN: 148728 Hom.: 275 Cov.: 34

Gnomad AFR AF: 0.0225

Gnomad AMI AF: 0.119

Gnomad AMR AF: 0.0436

Gnomad ASJ AF: 0.0367

Gnomad EAS AF: 0.000989

Gnomad SAS AF: 0.00877

Gnomad FIN AF: 0.0469

Gnomad MID AF: 0.0287

Gnomad NFE AF: 0.0801

Gnomad OTH AF: 0.0490

GnomAD2 exomes AF: 0.0479 AC: 11491 AN: 239650 AF XY: 0.0487

Gnomad AFR exome AF: 0.0204

Gnomad AMR exome AF: 0.0249

Gnomad ASJ exome AF: 0.0386

Gnomad EAS exome AF: 0.00144

Gnomad FIN exome AF: 0.0456

Gnomad NFE exome AF: 0.0780

Gnomad OTH exome AF: 0.0534

GnomAD4 exome AF: 0.0771 AC: 112389 AN: 1457136 Hom.: 5098 Cov.: 72 AF XY: 0.0749 AC XY: 54294 AN XY: 724608

African (AFR) AF: 0.0197 AC: 657 AN: 33392

American (AMR) AF: 0.0267 AC: 1182 AN: 44260

Ashkenazi Jewish (ASJ) AF: 0.0372 AC: 970 AN: 26068

East Asian (EAS) AF: 0.000985 AC: 39 AN: 39610

South Asian (SAS) AF: 0.0107 AC: 914 AN: 85676

European-Finnish (FIN) AF: 0.0470 AC: 2451 AN: 52148

Middle Eastern (MID) AF: 0.0344 AC: 198 AN: 5758

European-Non Finnish (NFE) AF: 0.0916 AC: 101716 AN: 1109992

Other (OTH) AF: 0.0708 AC: 4262 AN: 60232

GnomAD4 genome AF: 0.0525 AC: 7820 AN: 148846 Hom.: 275 Cov.: 34 AF XY: 0.0496 AC XY: 3596 AN XY: 72550

African (AFR) AF: 0.0225 AC: 895 AN: 39810

American (AMR) AF: 0.0436 AC: 641 AN: 14718

Ashkenazi Jewish (ASJ) AF: 0.0367 AC: 127 AN: 3460

East Asian (EAS) AF: 0.000992 AC: 5 AN: 5042

South Asian (SAS) AF: 0.00899 AC: 42 AN: 4672

European-Finnish (FIN) AF: 0.0469 AC: 485 AN: 10340

Middle Eastern (MID) AF: 0.0274 AC: 8 AN: 292

European-Non Finnish (NFE) AF: 0.0801 AC: 5410 AN: 67564

Other (OTH) AF: 0.0485 AC: 99 AN: 2042

Alfa AF: 0.0646 Hom.: 178

Bravo AF: 0.0494

Asia WGS AF: 0.00895 AC: 32 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.88
CADD	Benign	2.1
DANN	Benign	0.35
PhyloP100		-0.17
RBP_binding_hub_radar		0.0
RBP_regulation_power_radar		1.1
Mutation Taster		=100/0	polymorphism (auto)

Splicing

Name	Calibrated prediction	Score	Prediction
dbscSNV1_ADA	Benign	0.000019
dbscSNV1_RF	Benign	0.022
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: rs9263795; hg19: chr6-31132656;