rs3130501

Variant names:

• chr6-31168676-A-G
• rs3130501
• NM_002701.6:c.405+1540T>C

Your query was ambiguous. Multiple possible variants found:

• chr6-31168676-A-G
• chr6-31168676-A-T

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+1540T>C variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.78 in 152,172 control chromosomes in the GnomAD database, including 46,582 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 (46582 hom., cov: 32)
• Consequence: POU5F1 NM_002701.6 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.227
• Publications: 93 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=-0.99).
• BA1: GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.84 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
POU5F1	NM_002701.6	c.405+1540T>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+1540T>C		intron_variant	Intron 1 of 4	1	NM_002701.6	ENSP00000259915.7
POU5F1	ENST00000441888.7	c.-183-2629T>C		intron_variant	Intron 1 of 4	1		ENSP00000389359.2
POU5F1	ENST00000461401.1	n.443+1540T>C		intron_variant	Intron 1 of 1	1

Frequencies

GnomAD3 genomes AF: 0.780 AC: 118668 AN: 152054 Hom.: 46543 Cov.: 32

Gnomad AFR AF: 0.847

Gnomad AMI AF: 0.806

Gnomad AMR AF: 0.805

Gnomad ASJ AF: 0.862

Gnomad EAS AF: 0.678

Gnomad SAS AF: 0.688

Gnomad FIN AF: 0.749

Gnomad MID AF: 0.889

Gnomad NFE AF: 0.748

Gnomad OTH AF: 0.816

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

GnomAD4 genome AF: 0.780 AC: 118761 AN: 152172 Hom.: 46582 Cov.: 32 AF XY: 0.779 AC XY: 57972 AN XY: 74392

African (AFR) AF: 0.847 AC: 35171 AN: 41518

American (AMR) AF: 0.805 AC: 12298 AN: 15282

Ashkenazi Jewish (ASJ) AF: 0.862 AC: 2993 AN: 3472

East Asian (EAS) AF: 0.679 AC: 3504 AN: 5164

South Asian (SAS) AF: 0.687 AC: 3317 AN: 4830

European-Finnish (FIN) AF: 0.749 AC: 7935 AN: 10596

Middle Eastern (MID) AF: 0.884 AC: 260 AN: 294

European-Non Finnish (NFE) AF: 0.748 AC: 50826 AN: 67992

Other (OTH) AF: 0.815 AC: 1722 AN: 2112

Alfa AF: 0.762 Hom.: 180430

Bravo AF: 0.790

Asia WGS AF: 0.755 AC: 2629 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.99
CADD	Benign	1.2
DANN	Benign	0.51
PhyloP100		-0.23
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: rs3130501; hg19: chr6-31136453;