rs3130504

Variant names:

• chr6-31170060-A-G
• rs3130504
• NM_002701.6:c.405+156T>C

Your query was ambiguous. Multiple possible variants found:

• chr6-31170060-A-G
• chr6-31170060-A-T

Variant summary

Our verdict is Likely benign. The variant received -2 ACMG points: 2P and 4B. PM2 BP4_Strong

The NM_002701.6(POU5F1):​c.405+156T>C variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00000189 in 1,059,534 control chromosomes in the GnomAD database, with no homozygous occurrence. 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: not found (cov: 32)
  • Exomes 𝑓: 0.0000019 (0 hom.)
• Consequence: POU5F1 NM_002701.6 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -3.90
• Publications: 0 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: Likely_benign. The variant received -2 ACMG points.

• PM2: Very rare variant in population databases, with high coverage
• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.88).

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
POU5F1	NM_002701.6	c.405+156T>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+156T>C		intron_variant	Intron 1 of 4	1	NM_002701.6	ENSP00000259915.7
POU5F1	ENST00000441888.7	c.-183-4013T>C		intron_variant	Intron 1 of 4	1		ENSP00000389359.2
POU5F1	ENST00000461401.1	n.443+156T>C		intron_variant	Intron 1 of 1	1

Frequencies

GnomAD3 genomes Cov.: 32

GnomAD4 exome AF: 0.00000189 AC: 2 AN: 1059534 Hom.: 0 Cov.: 14 AF XY: 0.00000378 AC XY: 2 AN XY: 529634

African (AFR) AF: 0.00 AC: 0 AN: 24274

American (AMR) AF: 0.00 AC: 0 AN: 27398

Ashkenazi Jewish (ASJ) AF: 0.00 AC: 0 AN: 18466

East Asian (EAS) AF: 0.00 AC: 0 AN: 35130

South Asian (SAS) AF: 0.0000307 AC: 2 AN: 65148

European-Finnish (FIN) AF: 0.00 AC: 0 AN: 37886

Middle Eastern (MID) AF: 0.00 AC: 0 AN: 3216

European-Non Finnish (NFE) AF: 0.00 AC: 0 AN: 801756

Other (OTH) AF: 0.00 AC: 0 AN: 46260

GnomAD4 genome Cov.: 32

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.88
CADD	Benign	0.18
DANN	Benign	0.74
PhyloP100		-3.9

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: rs3130504; hg19: chr6-31137837;