chr6-31166166-C-A

Variant names:

• chr6-31166166-C-A
• rs3130932
• ENST00000471529.6:c.-302G>T

Variant summary

Our verdict is Benign. The variant received -10 ACMG points: 0P and 10B. BP4_Moderate BA1

The ENST00000471529.6(POU5F1):​c.-302G>T 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 0.667 in 1,605,810 control chromosomes in the GnomAD database, including 359,770 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 (36761 hom., cov: 32)
  • Exomes 𝑓: 0.66 (323009 hom.)
• Consequence: POU5F1 ENST00000471529.6 5_prime_UTR_premature_start_codon_gain
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 0.495
• Publications: 44 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 -10 ACMG points.

• BP4: Computational evidence support a benign effect (REVEL=0.017).
• BA1: GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.784 is higher than 0.05.

Variant Effect in Transcripts

ACMG analysis was done for transcript: ENST00000471529.6. 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.406-119G>T		intron	N/A	NP_002692.2
	POU5F1	NM_203289.6		c.-224G>T		5_prime_UTR_premature_start_codon_gain	Exon 1 of 4	NP_976034.4
	POU5F1	NM_001285986.2		c.-527G>T		5_prime_UTR_premature_start_codon_gain	Exon 1 of 3	NP_001272915.1

Ensembl Transcripts

Selected	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	POU5F1	ENST00000471529.6	TSL:1	c.-302G>T		5_prime_UTR_premature_start_codon_gain	Exon 1 of 4	ENSP00000425083.1
	POU5F1	ENST00000513407.1	TSL:1	c.-527G>T		5_prime_UTR_premature_start_codon_gain	Exon 1 of 3	ENSP00000475512.1
	POU5F1	ENST00000471529.6	TSL:1	c.-302G>T		5_prime_UTR	Exon 1 of 4	ENSP00000425083.1

Frequencies

GnomAD3 genomes AF: 0.691 AC: 104957 AN: 151930 Hom.: 36731 Cov.: 32

Gnomad AFR AF: 0.792

Gnomad AMI AF: 0.633

Gnomad AMR AF: 0.679

Gnomad ASJ AF: 0.727

Gnomad EAS AF: 0.635

Gnomad SAS AF: 0.570

Gnomad FIN AF: 0.569

Gnomad MID AF: 0.699

Gnomad NFE AF: 0.663

Gnomad OTH AF: 0.695

GnomAD2 exomes AF: 0.646 AC: 152795 AN: 236422 AF XY: 0.644

Gnomad AFR exome AF: 0.792

Gnomad AMR exome AF: 0.599

Gnomad ASJ exome AF: 0.719

Gnomad EAS exome AF: 0.654

Gnomad FIN exome AF: 0.577

Gnomad NFE exome AF: 0.664

Gnomad OTH exome AF: 0.672

GnomAD4 exome AF: 0.665 AC: 966642 AN: 1453762 Hom.: 323009 Cov.: 68 AF XY: 0.662 AC XY: 478343 AN XY: 722684

African (AFR) AF: 0.796 AC: 26491 AN: 33260

American (AMR) AF: 0.610 AC: 26568 AN: 43570

Ashkenazi Jewish (ASJ) AF: 0.718 AC: 18705 AN: 26036

East Asian (EAS) AF: 0.601 AC: 23702 AN: 39450

South Asian (SAS) AF: 0.583 AC: 49624 AN: 85094

European-Finnish (FIN) AF: 0.578 AC: 30627 AN: 52982

Middle Eastern (MID) AF: 0.690 AC: 3973 AN: 5762

European-Non Finnish (NFE) AF: 0.674 AC: 746396 AN: 1107520

Other (OTH) AF: 0.675 AC: 40556 AN: 60088

GnomAD4 genome AF: 0.691 AC: 105036 AN: 152048 Hom.: 36761 Cov.: 32 AF XY: 0.685 AC XY: 50877 AN XY: 74318

African (AFR) AF: 0.792 AC: 32849 AN: 41494

American (AMR) AF: 0.679 AC: 10364 AN: 15270

Ashkenazi Jewish (ASJ) AF: 0.727 AC: 2522 AN: 3470

East Asian (EAS) AF: 0.635 AC: 3282 AN: 5168

South Asian (SAS) AF: 0.568 AC: 2740 AN: 4820

European-Finnish (FIN) AF: 0.569 AC: 6004 AN: 10550

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

European-Non Finnish (NFE) AF: 0.663 AC: 45029 AN: 67956

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

Alfa AF: 0.670 Hom.: 66993

Bravo AF: 0.705

Asia WGS AF: 0.665 AC: 2310 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.79
CADD	Benign	13
DANN	Benign	0.83
PhyloP100		0.49
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: rs3130932; hg19: chr6-31133943; COSMIC: COSV52562806;