chr6-31170695-C-T

Variant names:

• chr6-31170695-C-T
• rs17197199
• ENST00000441888.7:c.-183-4648G>A

Variant summary

Our verdict is Benign. The variant received -10 ACMG points: 0P and 10B. BP4_Moderate BA1

The ENST00000441888.7(POU5F1):​c.-183-4648G>A variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0405 in 1,466,142 control chromosomes in the GnomAD database, including 2,348 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 0.072 (667 hom., cov: 32)
  • Exomes 𝑓: 0.037 (1681 hom.)
• Consequence: POU5F1 ENST00000441888.7 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 1.65
• Publications: 2 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 -10 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.37).
• BA1: GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.157 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

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	POU5F1	NM_002701.6	MANE Select	c.-75G>A		upstream_gene	N/A	NP_002692.2

Ensembl Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	POU5F1	ENST00000441888.7	TSL:1	c.-183-4648G>A		intron	N/A	ENSP00000389359.2	F2Z381
	POU5F1	ENST00000259915.13	TSL:1 MANE Select	c.-75G>A		upstream_gene	N/A	ENSP00000259915.7	Q01860-1
	POU5F1	ENST00000461401.1	TSL:1	n.-37G>A		upstream_gene	N/A

Frequencies

GnomAD3 genomes AF: 0.0721 AC: 10964 AN: 152084 Hom.: 665 Cov.: 32

Gnomad AFR AF: 0.158

Gnomad AMI AF: 0.0242

Gnomad AMR AF: 0.0404

Gnomad ASJ AF: 0.0196

Gnomad EAS AF: 0.167

Gnomad SAS AF: 0.0415

Gnomad FIN AF: 0.0528

Gnomad MID AF: 0.0443

Gnomad NFE AF: 0.0283

Gnomad OTH AF: 0.0709

GnomAD4 exome AF: 0.0368 AC: 48416 AN: 1313938 Hom.: 1681 Cov.: 32 AF XY: 0.0365 AC XY: 23332 AN XY: 638742

African (AFR) AF: 0.163 AC: 4732 AN: 28962

American (AMR) AF: 0.0334 AC: 802 AN: 24032

Ashkenazi Jewish (ASJ) AF: 0.0225 AC: 445 AN: 19746

East Asian (EAS) AF: 0.183 AC: 6427 AN: 35030

South Asian (SAS) AF: 0.0367 AC: 2419 AN: 65894

European-Finnish (FIN) AF: 0.0584 AC: 2551 AN: 43674

Middle Eastern (MID) AF: 0.0372 AC: 138 AN: 3706

European-Non Finnish (NFE) AF: 0.0271 AC: 28173 AN: 1038676

Other (OTH) AF: 0.0503 AC: 2729 AN: 54218

GnomAD4 genome AF: 0.0721 AC: 10975 AN: 152204 Hom.: 667 Cov.: 32 AF XY: 0.0728 AC XY: 5422 AN XY: 74434

African (AFR) AF: 0.158 AC: 6557 AN: 41508

American (AMR) AF: 0.0403 AC: 617 AN: 15302

Ashkenazi Jewish (ASJ) AF: 0.0196 AC: 68 AN: 3470

East Asian (EAS) AF: 0.166 AC: 859 AN: 5166

South Asian (SAS) AF: 0.0415 AC: 200 AN: 4814

European-Finnish (FIN) AF: 0.0528 AC: 561 AN: 10628

Middle Eastern (MID) AF: 0.0476 AC: 14 AN: 294

European-Non Finnish (NFE) AF: 0.0283 AC: 1926 AN: 68002

Other (OTH) AF: 0.0716 AC: 151 AN: 2110

Alfa AF: 0.0453 Hom.: 431

Bravo AF: 0.0775

Asia WGS AF: 0.115 AC: 398 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.37
CADD	Benign	20
DANN	Benign	0.89
PhyloP100		1.6
PromoterAI		-0.032	Neutral
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: rs17197199; hg19: chr6-31138472;