chr7-39108316-G-A

Variant names:

• chr7-39108316-G-A
• rs953874
• NM_001370959.1:c.277+22285G>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.277+22285G>A variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.282 in 150,398 control chromosomes in the GnomAD database, including 6,200 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 0.28 (6200 hom., cov: 30)
• Consequence: POU6F2 NM_001370959.1 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 0.263
• 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=-0.98).
• BA1: GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.541 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+22285G>A		intron	N/A	NP_001357888.1	A0A6E1XZL4
	POU6F2	NM_007252.4		c.190+22285G>A		intron	N/A	NP_009183.3	P78424-1
	POU6F2	NM_001166018.2		c.190+22285G>A		intron	N/A	NP_001159490.1	P78424-2

Ensembl Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	POU6F2	ENST00000518318.7	TSL:1 MANE Select	c.277+22285G>A		intron	N/A	ENSP00000430514.3	A0A6E1XZL4
	POU6F2	ENST00000403058.6	TSL:5	c.190+22285G>A		intron	N/A	ENSP00000384004.1	P78424-1
	POU6F2	ENST00000451021.5	TSL:4	n.329+22285G>A		intron	N/A

Frequencies

GnomAD3 genomes AF: 0.282 AC: 42326 AN: 150288 Hom.: 6198 Cov.: 30

Gnomad AFR AF: 0.243

Gnomad AMI AF: 0.302

Gnomad AMR AF: 0.299

Gnomad ASJ AF: 0.268

Gnomad EAS AF: 0.559

Gnomad SAS AF: 0.311

Gnomad FIN AF: 0.328

Gnomad MID AF: 0.218

Gnomad NFE AF: 0.272

Gnomad OTH AF: 0.270

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

GnomAD4 genome AF: 0.282 AC: 42353 AN: 150398 Hom.: 6200 Cov.: 30 AF XY: 0.288 AC XY: 21144 AN XY: 73316

African (AFR) AF: 0.242 AC: 9910 AN: 40882

American (AMR) AF: 0.299 AC: 4518 AN: 15100

Ashkenazi Jewish (ASJ) AF: 0.268 AC: 927 AN: 3462

East Asian (EAS) AF: 0.558 AC: 2840 AN: 5092

South Asian (SAS) AF: 0.312 AC: 1477 AN: 4738

European-Finnish (FIN) AF: 0.328 AC: 3359 AN: 10226

Middle Eastern (MID) AF: 0.227 AC: 65 AN: 286

European-Non Finnish (NFE) AF: 0.272 AC: 18422 AN: 67616

Other (OTH) AF: 0.268 AC: 561 AN: 2090

Alfa AF: 0.273 Hom.: 18440

Bravo AF: 0.280

Asia WGS AF: 0.418 AC: 1453 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.98
CADD	Benign	2.0
DANN	Benign	0.23
PhyloP100		0.26
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: rs953874; hg19: chr7-39147916;