chr6-31168889-A-G

Variant names:

• chr6-31168889-A-G
• rs3130502
• NM_002701.6:c.405+1327T>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+1327T>C variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.777 in 152,206 control chromosomes in the GnomAD database, including 46,203 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 0.78 (46203 hom., cov: 32)
• Consequence: POU5F1 NM_002701.6 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 0.248
• Publications: 32 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=-0.93).
• BA1: GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.839 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
POU5F1	NM_002701.6	c.405+1327T>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+1327T>C		intron_variant	Intron 1 of 4	1	NM_002701.6	ENSP00000259915.7
POU5F1	ENST00000441888.7	c.-183-2842T>C		intron_variant	Intron 1 of 4	1		ENSP00000389359.2
POU5F1	ENST00000461401.1	n.443+1327T>C		intron_variant	Intron 1 of 1	1

Frequencies

GnomAD3 genomes AF: 0.777 AC: 118193 AN: 152088 Hom.: 46166 Cov.: 32

Gnomad AFR AF: 0.847

Gnomad AMI AF: 0.805

Gnomad AMR AF: 0.797

Gnomad ASJ AF: 0.859

Gnomad EAS AF: 0.677

Gnomad SAS AF: 0.664

Gnomad FIN AF: 0.749

Gnomad MID AF: 0.864

Gnomad NFE AF: 0.745

Gnomad OTH AF: 0.808

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

GnomAD4 genome AF: 0.777 AC: 118284 AN: 152206 Hom.: 46203 Cov.: 32 AF XY: 0.775 AC XY: 57696 AN XY: 74412

African (AFR) AF: 0.847 AC: 35159 AN: 41520

American (AMR) AF: 0.797 AC: 12184 AN: 15296

Ashkenazi Jewish (ASJ) AF: 0.859 AC: 2981 AN: 3472

East Asian (EAS) AF: 0.677 AC: 3510 AN: 5182

South Asian (SAS) AF: 0.663 AC: 3200 AN: 4830

European-Finnish (FIN) AF: 0.749 AC: 7923 AN: 10582

Middle Eastern (MID) AF: 0.857 AC: 252 AN: 294

European-Non Finnish (NFE) AF: 0.745 AC: 50635 AN: 68006

Other (OTH) AF: 0.807 AC: 1707 AN: 2114

Alfa AF: 0.758 Hom.: 172951

Bravo AF: 0.787

Asia WGS AF: 0.743 AC: 2585 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.93
CADD	Benign	5.7
DANN	Benign	0.50
PhyloP100		0.25
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: rs3130502; hg19: chr6-31136666;