rs1949880

Variant names:

• chr7-39056788-T-C
• rs1949880
• NM_001370959.1:c.106-29072T>C

Variant summary

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

The NM_001370959.1(POU6F2):​c.106-29072T>C variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.316 in 151,354 control chromosomes in the GnomAD database, including 8,230 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 0.32 (8230 hom., cov: 29)
• Consequence: POU6F2 NM_001370959.1 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 0.425
• Publications: 4 publications found

Genes affected

POU6F2 (HGNC:21694): (POU class 6 homeobox 2) This gene encodes a member of the POU protein family characterized by the presence of a bipartite DNA binding domain, consisting of a POU-specific domain and a homeodomain, separated by a variable polylinker. The DNA binding domain may bind to DNA as monomers or as homo- and/or heterodimers, in a sequence-specific manner. The POU family members are transcriptional regulators, many of which are known to control cell type-specific differentiation pathways. This gene is a tumor suppressor involved in Wilms tumor (WT) predisposition. Alternatively spliced transcript variants encoding distinct isoforms have been found for this gene.[provided by RefSeq, Oct 2009]

POU6F2 Gene-Disease associations (from GenCC):

• Wilms tumor 5

  Inheritance: Unknown Classification: LIMITED Submitted by: Ambry Genetics

ACMG classification

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

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.92).
• BA1: GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.452 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
POU6F2	NM_001370959.1	c.106-29072T>C		intron_variant	Intron 1 of 9	ENST00000518318.7	NP_001357888.1
POU6F2	NM_007252.4	c.19-29072T>C		intron_variant	Intron 2 of 10		NP_009183.3
POU6F2	NM_001166018.2	c.19-29072T>C		intron_variant	Intron 2 of 10		NP_001159490.1
POU6F2	XM_047419843.1	c.19-29072T>C		intron_variant	Intron 1 of 8		XP_047275799.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
POU6F2	ENST00000518318.7	c.106-29072T>C		intron_variant	Intron 1 of 9	1	NM_001370959.1	ENSP00000430514.3

Frequencies

GnomAD3 genomes AF: 0.316 AC: 47838 AN: 151236 Hom.: 8206 Cov.: 29

Gnomad AFR AF: 0.457

Gnomad AMI AF: 0.345

Gnomad AMR AF: 0.266

Gnomad ASJ AF: 0.282

Gnomad EAS AF: 0.148

Gnomad SAS AF: 0.165

Gnomad FIN AF: 0.288

Gnomad MID AF: 0.405

Gnomad NFE AF: 0.271

Gnomad OTH AF: 0.326

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

GnomAD4 genome AF: 0.316 AC: 47897 AN: 151354 Hom.: 8230 Cov.: 29 AF XY: 0.313 AC XY: 23102 AN XY: 73906

African (AFR) AF: 0.457 AC: 18821 AN: 41140

American (AMR) AF: 0.265 AC: 4021 AN: 15158

Ashkenazi Jewish (ASJ) AF: 0.282 AC: 977 AN: 3466

East Asian (EAS) AF: 0.148 AC: 764 AN: 5150

South Asian (SAS) AF: 0.165 AC: 788 AN: 4790

European-Finnish (FIN) AF: 0.288 AC: 3021 AN: 10492

Middle Eastern (MID) AF: 0.381 AC: 112 AN: 294

European-Non Finnish (NFE) AF: 0.271 AC: 18383 AN: 67846

Other (OTH) AF: 0.330 AC: 696 AN: 2108

Alfa AF: 0.284 Hom.: 26931

Bravo AF: 0.323

Asia WGS AF: 0.207 AC: 720 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.92
CADD	Benign	4.4
DANN	Benign	0.71
PhyloP100		0.42
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: rs1949880; hg19: chr7-39096388;