ENST00000441888.7:c.-184+1202A>G

Variant names:

• chr6-31179417-T-C
• rs3130457
• ENST00000441888.7:c.-184+1202A>G

Variant summary

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

The ENST00000441888.7(POU5F1):​c.-184+1202A>G variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.21 in 152,034 control chromosomes in the GnomAD database, including 3,536 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 0.21 (3536 hom., cov: 31)
• Consequence: POU5F1 ENST00000441888.7 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.288
• 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]

PSORS1C3 (HGNC:17203): (psoriasis susceptibility 1 candidate 3)

ACMG classification

Our verdict: Benign. The variant received -12 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.96).
• BA1: GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.241 is higher than 0.05.

Variant Effect in Transcripts

ACMG analysis was done for transcript: ENST00000441888.7. 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
	PSORS1C3	NR_026816.2		n.293-1518A>G		intron	N/A
	PSORS1C3	NR_152828.1		n.293-1518A>G		intron	N/A
	PSORS1C3	NR_152829.1		n.293-1518A>G		intron	N/A

Ensembl Transcripts

Selected	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	POU5F1	ENST00000441888.7	TSL:1	c.-184+1202A>G		intron	N/A	ENSP00000389359.2
	PSORS1C3	ENST00000412143.2	TSL:1	n.94-1518A>G		intron	N/A

Frequencies

GnomAD3 genomes AF: 0.211 AC: 31983 AN: 151916 Hom.: 3532 Cov.: 31

Gnomad AFR AF: 0.245

Gnomad AMI AF: 0.342

Gnomad AMR AF: 0.149

Gnomad ASJ AF: 0.260

Gnomad EAS AF: 0.0399

Gnomad SAS AF: 0.115

Gnomad FIN AF: 0.137

Gnomad MID AF: 0.241

Gnomad NFE AF: 0.230

Gnomad OTH AF: 0.207

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

GnomAD4 genome AF: 0.210 AC: 31996 AN: 152034 Hom.: 3536 Cov.: 31 AF XY: 0.201 AC XY: 14950 AN XY: 74326

African (AFR) AF: 0.245 AC: 10165 AN: 41414

American (AMR) AF: 0.148 AC: 2269 AN: 15280

Ashkenazi Jewish (ASJ) AF: 0.260 AC: 900 AN: 3464

East Asian (EAS) AF: 0.0400 AC: 207 AN: 5178

South Asian (SAS) AF: 0.114 AC: 549 AN: 4822

European-Finnish (FIN) AF: 0.137 AC: 1449 AN: 10598

Middle Eastern (MID) AF: 0.231 AC: 68 AN: 294

European-Non Finnish (NFE) AF: 0.230 AC: 15650 AN: 67970

Other (OTH) AF: 0.203 AC: 427 AN: 2102

Alfa AF: 0.223 Hom.: 13902

Bravo AF: 0.213

Asia WGS AF: 0.0790 AC: 278 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.96
CADD	Benign	8.1
DANN	Benign	0.69
PhyloP100		-0.29
Mutation Taster		=100/0	polymorphism (auto)

Splicing

Find out detailed SpliceAI scores and Pangolin per-transcript scores at spliceailookup.broadinstitute.org

Other links and lift over

dbSNP: rs3130457; hg19: chr6-31147194;