6-31170600-C-T

Variant names:

• chr6-31170600-C-T
• rs2077010
• NM_002701.6:c.21G>A

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.21G>A​(p.Ser7Ser) variant causes a synonymous change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.433 in 1,556,262 control chromosomes in the GnomAD database, including 147,317 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 0.43 (14081 hom., cov: 33)
  • Exomes 𝑓: 0.43 (133236 hom.)
• Consequence: POU5F1 NM_002701.6 synonymous
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -2.02
• 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=-0.5).
• BP7: Synonymous conserved (PhyloP=-2.03 with no splicing effect.
• BA1: GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.452 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
POU5F1	NM_002701.6	c.21G>A	p.Ser7Ser	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.21G>A	p.Ser7Ser	synonymous_variant	Exon 1 of 5	1	NM_002701.6	ENSP00000259915.7
POU5F1	ENST00000461401.1	n.59G>A		non_coding_transcript_exon_variant	Exon 1 of 2	1
POU5F1	ENST00000441888.7	c.-183-4553G>A		intron_variant	Intron 1 of 4	1		ENSP00000389359.2

Frequencies

GnomAD3 genomes AF: 0.429 AC: 65198 AN: 151892 Hom.: 14076 Cov.: 33

Gnomad AFR AF: 0.458

Gnomad AMI AF: 0.446

Gnomad AMR AF: 0.445

Gnomad ASJ AF: 0.374

Gnomad EAS AF: 0.378

Gnomad SAS AF: 0.376

Gnomad FIN AF: 0.361

Gnomad MID AF: 0.449

Gnomad NFE AF: 0.430

Gnomad OTH AF: 0.404

GnomAD2 exomes AF: 0.399 AC: 64544 AN: 161740 AF XY: 0.397

Gnomad AFR exome AF: 0.447

Gnomad AMR exome AF: 0.427

Gnomad ASJ exome AF: 0.375

Gnomad EAS exome AF: 0.355

Gnomad FIN exome AF: 0.362

Gnomad NFE exome AF: 0.411

Gnomad OTH exome AF: 0.416

GnomAD4 exome AF: 0.433 AC: 608324 AN: 1404252 Hom.: 133236 Cov.: 86 AF XY: 0.430 AC XY: 298289 AN XY: 693424

African (AFR) AF: 0.455 AC: 14605 AN: 32106

American (AMR) AF: 0.428 AC: 15239 AN: 35574

Ashkenazi Jewish (ASJ) AF: 0.385 AC: 9585 AN: 24900

East Asian (EAS) AF: 0.358 AC: 13276 AN: 37034

South Asian (SAS) AF: 0.381 AC: 30467 AN: 79878

European-Finnish (FIN) AF: 0.365 AC: 17849 AN: 48850

Middle Eastern (MID) AF: 0.410 AC: 1960 AN: 4780

European-Non Finnish (NFE) AF: 0.444 AC: 480630 AN: 1083004

Other (OTH) AF: 0.425 AC: 24713 AN: 58126

GnomAD4 genome AF: 0.429 AC: 65225 AN: 152010 Hom.: 14081 Cov.: 33 AF XY: 0.424 AC XY: 31505 AN XY: 74318

African (AFR) AF: 0.457 AC: 18957 AN: 41452

American (AMR) AF: 0.445 AC: 6798 AN: 15288

Ashkenazi Jewish (ASJ) AF: 0.374 AC: 1299 AN: 3470

East Asian (EAS) AF: 0.379 AC: 1947 AN: 5138

South Asian (SAS) AF: 0.374 AC: 1801 AN: 4818

European-Finnish (FIN) AF: 0.361 AC: 3819 AN: 10590

Middle Eastern (MID) AF: 0.439 AC: 129 AN: 294

European-Non Finnish (NFE) AF: 0.430 AC: 29220 AN: 67944

Other (OTH) AF: 0.403 AC: 850 AN: 2108

Alfa AF: 0.416 Hom.: 4346

Bravo AF: 0.437

Asia WGS AF: 0.397 AC: 1379 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.50
CADD	Benign	6.7
DANN	Benign	0.93
PhyloP100		-2.0
PromoterAI		-0.046	Neutral
Mutation Taster		=97/3	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: rs2077010; hg19: chr6-31138377; COSMIC: COSV107275219; COSMIC: COSV107275219;