6-31166117-G-C

Variant names:

• chr6-31166117-G-C
• rs9501063
• ENST00000471529.6:c.-253C>G

Variant summary

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

The NM_203289.6(POU5F1):​c.-175C>G variant causes a 5 prime UTR change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0412 in 1,613,976 control chromosomes in the GnomAD database, including 2,609 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 0.073 (674 hom., cov: 32)
  • Exomes 𝑓: 0.038 (1935 hom.)
• Consequence: POU5F1 NM_203289.6 5_prime_UTR
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.758
• Publications: 13 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=-0.89).
• BA1: GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.158 is higher than 0.05.

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_203289.6. You can select a different transcript below to see updated ACMG assignments.

RefSeq Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	POU5F1	NM_002701.6	MANE Select	c.406-70C>G		intron	N/A	NP_002692.2
	POU5F1	NM_203289.6		c.-175C>G		5_prime_UTR	Exon 1 of 4	NP_976034.4	M1S623
	POU5F1	NM_001285986.2		c.-478C>G		5_prime_UTR	Exon 1 of 3	NP_001272915.1	F2Z381

Ensembl Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	POU5F1	ENST00000471529.6	TSL:1	c.-253C>G		5_prime_UTR	Exon 1 of 4	ENSP00000425083.1	F2Z381
	POU5F1	ENST00000513407.1	TSL:1	c.-478C>G		5_prime_UTR	Exon 1 of 3	ENSP00000475512.1	F2Z381
	POU5F1	ENST00000259915.13	TSL:1 MANE Select	c.406-70C>G		intron	N/A	ENSP00000259915.7	Q01860-1

Frequencies

GnomAD3 genomes AF: 0.0732 AC: 11125 AN: 152064 Hom.: 672 Cov.: 32

Gnomad AFR AF: 0.159

Gnomad AMI AF: 0.0241

Gnomad AMR AF: 0.0415

Gnomad ASJ AF: 0.0444

Gnomad EAS AF: 0.168

Gnomad SAS AF: 0.0424

Gnomad FIN AF: 0.0527

Gnomad MID AF: 0.0443

Gnomad NFE AF: 0.0287

Gnomad OTH AF: 0.0738

GnomAD2 exomes AF: 0.0519 AC: 13028 AN: 250802 AF XY: 0.0494

Gnomad AFR exome AF: 0.160

Gnomad AMR exome AF: 0.0265

Gnomad ASJ exome AF: 0.0501

Gnomad EAS exome AF: 0.177

Gnomad FIN exome AF: 0.0561

Gnomad NFE exome AF: 0.0276

Gnomad OTH exome AF: 0.0478

GnomAD4 exome AF: 0.0379 AC: 55344 AN: 1461794 Hom.: 1935 Cov.: 39 AF XY: 0.0374 AC XY: 27176 AN XY: 727198

African (AFR) AF: 0.161 AC: 5401 AN: 33480

American (AMR) AF: 0.0295 AC: 1318 AN: 44718

Ashkenazi Jewish (ASJ) AF: 0.0489 AC: 1278 AN: 26134

East Asian (EAS) AF: 0.184 AC: 7295 AN: 39690

South Asian (SAS) AF: 0.0366 AC: 3152 AN: 86230

European-Finnish (FIN) AF: 0.0579 AC: 3092 AN: 53414

Middle Eastern (MID) AF: 0.0385 AC: 222 AN: 5768

European-Non Finnish (NFE) AF: 0.0273 AC: 30409 AN: 1111972

Other (OTH) AF: 0.0526 AC: 3177 AN: 60388

GnomAD4 genome AF: 0.0732 AC: 11135 AN: 152182 Hom.: 674 Cov.: 32 AF XY: 0.0740 AC XY: 5507 AN XY: 74406

African (AFR) AF: 0.158 AC: 6571 AN: 41496

American (AMR) AF: 0.0415 AC: 634 AN: 15282

Ashkenazi Jewish (ASJ) AF: 0.0444 AC: 154 AN: 3470

East Asian (EAS) AF: 0.167 AC: 865 AN: 5180

South Asian (SAS) AF: 0.0424 AC: 204 AN: 4808

European-Finnish (FIN) AF: 0.0527 AC: 559 AN: 10612

Middle Eastern (MID) AF: 0.0476 AC: 14 AN: 294

European-Non Finnish (NFE) AF: 0.0287 AC: 1955 AN: 68018

Other (OTH) AF: 0.0744 AC: 157 AN: 2110

Alfa AF: 0.0409 Hom.: 170

Bravo AF: 0.0784

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.89
CADD	Benign	0.39
DANN	Benign	0.46
PhyloP100		-0.76
Mutation Taster		=300/0	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: rs9501063; hg19: chr6-31133894; COSMIC: COSV52565467; COSMIC: COSV52565467;