NM_001370959.1:c.277+30927C>T

Variant names:

• chr7-39116958-C-T
• rs1525791
• NM_001370959.1:c.277+30927C>T

Variant summary

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

The NM_001370959.1(POU6F2):​c.277+30927C>T variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.134 in 152,122 control chromosomes in the GnomAD database, including 1,412 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 0.13 (1412 hom., cov: 32)
• Consequence: POU6F2 NM_001370959.1 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -2.26
• Publications: 5 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=-0.95).
• BA1: GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.148 is higher than 0.05.

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_001370959.1. 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
	POU6F2	NM_001370959.1	MANE Select	c.277+30927C>T		intron	N/A	NP_001357888.1
	POU6F2	NM_007252.4		c.190+30927C>T		intron	N/A	NP_009183.3
	POU6F2	NM_001166018.2		c.190+30927C>T		intron	N/A	NP_001159490.1

Ensembl Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	POU6F2	ENST00000518318.7	TSL:1 MANE Select	c.277+30927C>T		intron	N/A	ENSP00000430514.3
	POU6F2	ENST00000403058.6	TSL:5	c.190+30927C>T		intron	N/A	ENSP00000384004.1
	POU6F2	ENST00000451021.5	TSL:4	n.329+30927C>T		intron	N/A

Frequencies

GnomAD3 genomes AF: 0.134 AC: 20403 AN: 152004 Hom.: 1414 Cov.: 32

Gnomad AFR AF: 0.151

Gnomad AMI AF: 0.269

Gnomad AMR AF: 0.103

Gnomad ASJ AF: 0.117

Gnomad EAS AF: 0.131

Gnomad SAS AF: 0.0519

Gnomad FIN AF: 0.136

Gnomad MID AF: 0.165

Gnomad NFE AF: 0.136

Gnomad OTH AF: 0.139

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

GnomAD4 genome AF: 0.134 AC: 20393 AN: 152122 Hom.: 1412 Cov.: 32 AF XY: 0.132 AC XY: 9785 AN XY: 74382

African (AFR) AF: 0.151 AC: 6266 AN: 41474

American (AMR) AF: 0.102 AC: 1561 AN: 15276

Ashkenazi Jewish (ASJ) AF: 0.117 AC: 405 AN: 3472

East Asian (EAS) AF: 0.130 AC: 675 AN: 5176

South Asian (SAS) AF: 0.0517 AC: 249 AN: 4816

European-Finnish (FIN) AF: 0.136 AC: 1434 AN: 10574

Middle Eastern (MID) AF: 0.153 AC: 45 AN: 294

European-Non Finnish (NFE) AF: 0.136 AC: 9224 AN: 68016

Other (OTH) AF: 0.137 AC: 289 AN: 2112

Alfa AF: 0.131 Hom.: 803

Bravo AF: 0.135

Asia WGS AF: 0.0880 AC: 306 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.95
CADD	Benign	0.16
DANN	Benign	0.47
PhyloP100		-2.3
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: rs1525791; hg19: chr7-39156558;