rs60464047

Variant names:

• chr7-39378939-T-A
• rs60464047
• NM_001370959.1:c.973-27661T>A

Variant summary

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

The NM_001370959.1(POU6F2):​c.973-27661T>A variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.131 in 152,182 control chromosomes in the GnomAD database, including 1,447 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 (1447 hom., cov: 32)
• Consequence: POU6F2 NM_001370959.1 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 0.303
• 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=-0.63).
• BA1: GnomAd4 highest subpopulation (AMR) allele frequency at 95% confidence interval = 0.199 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

Selected	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	POU6F2	NM_001370959.1	MANE Select	c.973-27661T>A		intron	N/A	NP_001357888.1
	POU6F2	NM_007252.4		c.886-27661T>A		intron	N/A	NP_009183.3
	POU6F2	NM_001166018.2		c.886-27661T>A		intron	N/A	NP_001159490.1

Ensembl Transcripts

Selected	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	POU6F2	ENST00000518318.7	TSL:1 MANE Select	c.973-27661T>A		intron	N/A	ENSP00000430514.3
	POU6F2	ENST00000403058.6	TSL:5	c.886-27661T>A		intron	N/A	ENSP00000384004.1
	POU6F2	ENST00000520104.5	TSL:5	n.943-27661T>A		intron	N/A

Frequencies

GnomAD3 genomes AF: 0.131 AC: 19862 AN: 152064 Hom.: 1447 Cov.: 32

Gnomad AFR AF: 0.0819

Gnomad AMI AF: 0.0899

Gnomad AMR AF: 0.205

Gnomad ASJ AF: 0.173

Gnomad EAS AF: 0.0249

Gnomad SAS AF: 0.126

Gnomad FIN AF: 0.131

Gnomad MID AF: 0.155

Gnomad NFE AF: 0.150

Gnomad OTH AF: 0.147

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

GnomAD4 genome AF: 0.131 AC: 19865 AN: 152182 Hom.: 1447 Cov.: 32 AF XY: 0.132 AC XY: 9834 AN XY: 74414

African (AFR) AF: 0.0819 AC: 3400 AN: 41530

American (AMR) AF: 0.205 AC: 3135 AN: 15286

Ashkenazi Jewish (ASJ) AF: 0.173 AC: 599 AN: 3464

East Asian (EAS) AF: 0.0248 AC: 128 AN: 5166

South Asian (SAS) AF: 0.126 AC: 607 AN: 4820

European-Finnish (FIN) AF: 0.131 AC: 1385 AN: 10590

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

European-Non Finnish (NFE) AF: 0.150 AC: 10179 AN: 68006

Other (OTH) AF: 0.144 AC: 305 AN: 2114

Alfa AF: 0.138 Hom.: 194

Bravo AF: 0.135

Asia WGS AF: 0.0850 AC: 299 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.63
CADD	Benign	5.3
DANN	Benign	0.85
PhyloP100		0.30
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: rs60464047; hg19: chr7-39418538;