rs2106074

Variant names:

• chr6-31165732-G-A
• rs2106074
• ENST00000461401.1:n.759C>T

Your query was ambiguous. Multiple possible variants found:

• chr6-31165732-G-A
• chr6-31165732-G-C
• chr6-31165732-G-T

Variant summary

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

The ENST00000461401.1(POU5F1):​n.759C>T variant causes a non coding transcript exon change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.667 in 1,593,866 control chromosomes in the GnomAD database, including 357,154 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 (36726 hom., cov: 31)
  • Exomes 𝑓: 0.66 (320428 hom.)
• Consequence: POU5F1 ENST00000461401.1 non_coding_transcript_exon
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 0.115
• Publications: 29 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=-0.85).
• BA1: GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.784 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
POU5F1	NM_002701.6	c.527-31C>T		intron_variant	Intron 2 of 4	ENST00000259915.13	NP_002692.2
POU5F1	NM_001285986.2	c.-93C>T		5_prime_UTR_variant	Exon 1 of 3		NP_001272915.1
POU5F1	NM_001173531.3	c.17-31C>T		intron_variant	Intron 2 of 4		NP_001167002.1
POU5F1	NM_203289.6	c.17-31C>T		intron_variant	Intron 1 of 3		NP_976034.4

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
POU5F1	ENST00000259915.13	c.527-31C>T		intron_variant	Intron 2 of 4	1	NM_002701.6	ENSP00000259915.7

Frequencies

GnomAD3 genomes AF: 0.691 AC: 104866 AN: 151810 Hom.: 36696 Cov.: 31

Gnomad AFR AF: 0.791

Gnomad AMI AF: 0.632

Gnomad AMR AF: 0.679

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

GnomAD2 exomes AF: 0.642 AC: 139266 AN: 216910 AF XY: 0.639

Gnomad AFR exome AF: 0.789

Gnomad AMR exome AF: 0.600

Gnomad ASJ exome AF: 0.718

Gnomad EAS exome AF: 0.652

Gnomad FIN exome AF: 0.573

Gnomad NFE exome AF: 0.658

Gnomad OTH exome AF: 0.671

GnomAD4 exome AF: 0.665 AC: 958656 AN: 1441938 Hom.: 320428 Cov.: 72 AF XY: 0.662 AC XY: 473437 AN XY: 715426

African (AFR) AF: 0.796 AC: 26531 AN: 33322

American (AMR) AF: 0.610 AC: 24696 AN: 40464

Ashkenazi Jewish (ASJ) AF: 0.718 AC: 18428 AN: 25664

East Asian (EAS) AF: 0.601 AC: 23579 AN: 39254

South Asian (SAS) AF: 0.583 AC: 48918 AN: 83954

European-Finnish (FIN) AF: 0.577 AC: 30129 AN: 52238

Middle Eastern (MID) AF: 0.690 AC: 3962 AN: 5742

European-Non Finnish (NFE) AF: 0.674 AC: 742081 AN: 1101522

Other (OTH) AF: 0.675 AC: 40332 AN: 59778

GnomAD4 genome AF: 0.691 AC: 104945 AN: 151928 Hom.: 36726 Cov.: 31 AF XY: 0.685 AC XY: 50820 AN XY: 74242

African (AFR) AF: 0.792 AC: 32790 AN: 41424

American (AMR) AF: 0.679 AC: 10359 AN: 15266

Ashkenazi Jewish (ASJ) AF: 0.727 AC: 2521 AN: 3470

East Asian (EAS) AF: 0.635 AC: 3270 AN: 5152

South Asian (SAS) AF: 0.568 AC: 2731 AN: 4808

European-Finnish (FIN) AF: 0.569 AC: 5993 AN: 10534

Middle Eastern (MID) AF: 0.694 AC: 204 AN: 294

European-Non Finnish (NFE) AF: 0.663 AC: 45036 AN: 67954

Other (OTH) AF: 0.693 AC: 1465 AN: 2114

Alfa AF: 0.678 Hom.: 72889

Bravo AF: 0.705

Asia WGS AF: 0.664 AC: 2309 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.85
CADD	Benign	1.9
DANN	Benign	0.53
PhyloP100		0.12
RBP_binding_hub_radar		0.0
RBP_regulation_power_radar		1.1
Mutation Taster		=100/0	polymorphism (auto)

Splicing

Name	Calibrated prediction	Score	Prediction
SpliceAI score (max)		0.010		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: rs2106074; hg19: chr6-31133509; COSMIC: COSV52565450; COSMIC: COSV52565450;