NM_002701.6:c.27C>T

Variant names:

• chr6-31170594-G-A
• rs1265160
• NM_002701.6:c.27C>T

Variant summary

Our verdict is Benign. The variant received -13 ACMG points: 0P and 13B. BP4_Strong BP7 BA1

The NM_002701.6(POU5F1):​c.27C>T​(p.Phe9Phe) variant causes a synonymous change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.13 in 1,560,906 control chromosomes in the GnomAD database, including 14,651 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 0.14 (1715 hom., cov: 33)
  • Exomes 𝑓: 0.13 (12936 hom.)
• Consequence: POU5F1 NM_002701.6 synonymous
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -2.49
• Publications: 9 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]

ACMG classification

Our verdict: Benign. The variant received -13 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.62).
• BP7: Synonymous conserved (PhyloP=-2.49 with no splicing effect.
• BA1: GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.29 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
POU5F1	NM_002701.6	c.27C>T	p.Phe9Phe	synonymous_variant	Exon 1 of 5	ENST00000259915.13	NP_002692.2

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
POU5F1	ENST00000259915.13	c.27C>T	p.Phe9Phe	synonymous_variant	Exon 1 of 5	1	NM_002701.6	ENSP00000259915.7
POU5F1	ENST00000461401.1	n.65C>T		non_coding_transcript_exon_variant	Exon 1 of 2	1
POU5F1	ENST00000441888.7	c.-183-4547C>T		intron_variant	Intron 1 of 4	1		ENSP00000389359.2

Frequencies

GnomAD3 genomes AF: 0.144 AC: 21820 AN: 152032 Hom.: 1711 Cov.: 33

Gnomad AFR AF: 0.153

Gnomad AMI AF: 0.0637

Gnomad AMR AF: 0.204

Gnomad ASJ AF: 0.0533

Gnomad EAS AF: 0.302

Gnomad SAS AF: 0.127

Gnomad FIN AF: 0.127

Gnomad MID AF: 0.0823

Gnomad NFE AF: 0.123

Gnomad OTH AF: 0.125

GnomAD2 exomes AF: 0.138 AC: 22752 AN: 164462 AF XY: 0.132

Gnomad AFR exome AF: 0.144

Gnomad AMR exome AF: 0.209

Gnomad ASJ exome AF: 0.0476

Gnomad EAS exome AF: 0.284

Gnomad FIN exome AF: 0.132

Gnomad NFE exome AF: 0.111

Gnomad OTH exome AF: 0.122

GnomAD4 exome AF: 0.129 AC: 181581 AN: 1408756 Hom.: 12936 Cov.: 84 AF XY: 0.126 AC XY: 88020 AN XY: 696150

African (AFR) AF: 0.146 AC: 4700 AN: 32244

American (AMR) AF: 0.205 AC: 7386 AN: 36040

Ashkenazi Jewish (ASJ) AF: 0.0520 AC: 1301 AN: 25020

East Asian (EAS) AF: 0.302 AC: 11246 AN: 37230

South Asian (SAS) AF: 0.106 AC: 8520 AN: 80206

European-Finnish (FIN) AF: 0.132 AC: 6475 AN: 49048

Middle Eastern (MID) AF: 0.0618 AC: 300 AN: 4852

European-Non Finnish (NFE) AF: 0.124 AC: 134656 AN: 1085826

Other (OTH) AF: 0.120 AC: 6997 AN: 58290

GnomAD4 genome AF: 0.144 AC: 21838 AN: 152150 Hom.: 1715 Cov.: 33 AF XY: 0.146 AC XY: 10854 AN XY: 74388

African (AFR) AF: 0.152 AC: 6321 AN: 41506

American (AMR) AF: 0.205 AC: 3130 AN: 15288

Ashkenazi Jewish (ASJ) AF: 0.0533 AC: 185 AN: 3470

East Asian (EAS) AF: 0.303 AC: 1557 AN: 5144

South Asian (SAS) AF: 0.127 AC: 611 AN: 4824

European-Finnish (FIN) AF: 0.127 AC: 1345 AN: 10600

Middle Eastern (MID) AF: 0.0782 AC: 23 AN: 294

European-Non Finnish (NFE) AF: 0.123 AC: 8339 AN: 68008

Other (OTH) AF: 0.128 AC: 269 AN: 2106

Alfa AF: 0.116 Hom.: 398

Bravo AF: 0.149

Asia WGS AF: 0.206 AC: 715 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.62
CADD	Benign	4.1
DANN	Benign	0.92
PhyloP100		-2.5
PromoterAI		-0.0098	Neutral
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: rs1265160; hg19: chr6-31138371; COSMIC: COSV107275218; COSMIC: COSV107275218;