rs17840029

Variant names:

• chr6-31168975-A-G
• rs17840029
• NM_002701.6:c.405+1241T>C

Variant summary

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

The NM_002701.6(POU5F1):​c.405+1241T>C variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0423 in 152,290 control chromosomes in the GnomAD database, including 215 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 0.042 (215 hom., cov: 33)
• Consequence: POU5F1 NM_002701.6 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -2.35
• Publications: 1 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 -12 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.91).
• BA1: GnomAd4 highest subpopulation (SAS) allele frequency at 95% confidence interval = 0.077 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
POU5F1	NM_002701.6	c.405+1241T>C		intron_variant	Intron 1 of 4	ENST00000259915.13	NP_002692.2

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
POU5F1	ENST00000259915.13	c.405+1241T>C		intron_variant	Intron 1 of 4	1	NM_002701.6	ENSP00000259915.7
POU5F1	ENST00000441888.7	c.-183-2928T>C		intron_variant	Intron 1 of 4	1		ENSP00000389359.2
POU5F1	ENST00000461401.1	n.443+1241T>C		intron_variant	Intron 1 of 1	1

Frequencies

GnomAD3 genomes AF: 0.0423 AC: 6441 AN: 152172 Hom.: 214 Cov.: 33

Gnomad AFR AF: 0.0158

Gnomad AMI AF: 0.0285

Gnomad AMR AF: 0.0590

Gnomad ASJ AF: 0.215

Gnomad EAS AF: 0.0127

Gnomad SAS AF: 0.0843

Gnomad FIN AF: 0.0395

Gnomad MID AF: 0.0886

Gnomad NFE AF: 0.0452

Gnomad OTH AF: 0.0550

We have no GnomAD4 exomes data on this position. Probably position not covered by the project.

GnomAD4 genome AF: 0.0423 AC: 6438 AN: 152290 Hom.: 215 Cov.: 33 AF XY: 0.0435 AC XY: 3240 AN XY: 74468

African (AFR) AF: 0.0158 AC: 656 AN: 41560

American (AMR) AF: 0.0589 AC: 901 AN: 15308

Ashkenazi Jewish (ASJ) AF: 0.215 AC: 748 AN: 3472

East Asian (EAS) AF: 0.0129 AC: 67 AN: 5190

South Asian (SAS) AF: 0.0837 AC: 403 AN: 4814

European-Finnish (FIN) AF: 0.0395 AC: 419 AN: 10608

Middle Eastern (MID) AF: 0.0884 AC: 26 AN: 294

European-Non Finnish (NFE) AF: 0.0452 AC: 3074 AN: 68018

Other (OTH) AF: 0.0558 AC: 118 AN: 2114

Alfa AF: 0.0481 Hom.: 348

Bravo AF: 0.0424

Asia WGS AF: 0.0530 AC: 184 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.91
CADD	Benign	0.15
DANN	Benign	0.71
PhyloP100		-2.3
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: rs17840029; hg19: chr6-31136752;