rs1062630

Variant names:

• chr6-31170330-G-A
• rs1062630
• NM_002701.6:c.291C>T

Variant summary

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

The ENST00000259915.13(POU5F1):​c.291C>T​(p.Gly97Gly) variant causes a synonymous change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.227 in 1,612,544 control chromosomes in the GnomAD database, including 44,585 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as (no stars).

• Frequency:
  • Genomes: 𝑓 0.22 (3905 hom., cov: 34)
  • Exomes 𝑓: 0.23 (40680 hom.)
• Consequence: POU5F1 ENST00000259915.13 synonymous
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.220
• Publications: 19 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=-0.69).
• BP7: Synonymous conserved (PhyloP=-0.22 with no splicing effect.
• BA1: GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.263 is higher than 0.05.

Variant Effect in Transcripts

ACMG analysis was done for transcript: ENST00000259915.13. 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.291C>T	p.Gly97Gly	synonymous	Exon 1 of 5	NP_002692.2

Ensembl Transcripts

Selected	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	POU5F1	ENST00000259915.13	TSL:1 MANE Select	c.291C>T	p.Gly97Gly	synonymous	Exon 1 of 5	ENSP00000259915.7
	POU5F1	ENST00000461401.1	TSL:1	n.329C>T		non_coding_transcript_exon	Exon 1 of 2
	POU5F1	ENST00000441888.7	TSL:1	c.-183-4283C>T		intron	N/A	ENSP00000389359.2

Frequencies

GnomAD3 genomes AF: 0.220 AC: 33515 AN: 152052 Hom.: 3900 Cov.: 34

Gnomad AFR AF: 0.267

Gnomad AMI AF: 0.341

Gnomad AMR AF: 0.160

Gnomad ASJ AF: 0.268

Gnomad EAS AF: 0.0408

Gnomad SAS AF: 0.129

Gnomad FIN AF: 0.137

Gnomad MID AF: 0.263

Gnomad NFE AF: 0.235

Gnomad OTH AF: 0.215

GnomAD2 exomes AF: 0.182 AC: 44705 AN: 245770 AF XY: 0.182

Gnomad AFR exome AF: 0.268

Gnomad AMR exome AF: 0.123

Gnomad ASJ exome AF: 0.282

Gnomad EAS exome AF: 0.0319

Gnomad FIN exome AF: 0.135

Gnomad NFE exome AF: 0.224

Gnomad OTH exome AF: 0.201

GnomAD4 exome AF: 0.228 AC: 333211 AN: 1460374 Hom.: 40680 Cov.: 47 AF XY: 0.225 AC XY: 163654 AN XY: 726490

African (AFR) AF: 0.271 AC: 9081 AN: 33464

American (AMR) AF: 0.127 AC: 5668 AN: 44712

Ashkenazi Jewish (ASJ) AF: 0.283 AC: 7406 AN: 26124

East Asian (EAS) AF: 0.0222 AC: 882 AN: 39700

South Asian (SAS) AF: 0.140 AC: 12095 AN: 86234

European-Finnish (FIN) AF: 0.139 AC: 7265 AN: 52342

Middle Eastern (MID) AF: 0.231 AC: 1305 AN: 5652

European-Non Finnish (NFE) AF: 0.248 AC: 275466 AN: 1111798

Other (OTH) AF: 0.233 AC: 14043 AN: 60348

GnomAD4 genome AF: 0.220 AC: 33529 AN: 152170 Hom.: 3905 Cov.: 34 AF XY: 0.211 AC XY: 15729 AN XY: 74428

African (AFR) AF: 0.267 AC: 11093 AN: 41510

American (AMR) AF: 0.159 AC: 2437 AN: 15300

Ashkenazi Jewish (ASJ) AF: 0.268 AC: 927 AN: 3464

East Asian (EAS) AF: 0.0409 AC: 212 AN: 5178

South Asian (SAS) AF: 0.129 AC: 621 AN: 4832

European-Finnish (FIN) AF: 0.137 AC: 1455 AN: 10614

Middle Eastern (MID) AF: 0.255 AC: 75 AN: 294

European-Non Finnish (NFE) AF: 0.235 AC: 15952 AN: 67958

Other (OTH) AF: 0.212 AC: 447 AN: 2112

Alfa AF: 0.227 Hom.: 2603

Bravo AF: 0.224

Asia WGS AF: 0.0840 AC: 294 AN: 3478

EpiCase AF: 0.238

EpiControl AF: 0.225

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.69
CADD	Benign	6.1
DANN	Benign	0.86
PhyloP100		-0.22
PromoterAI		0.00080	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: rs1062630; hg19: chr6-31138107; COSMIC: COSV52563392; COSMIC: COSV52563392;