Genetic Variant POU6F2:c.1114-7C>T (chr7-39433070-C-T) – ACMG Classification: Benign (-11 pts)

Variant summary

Our verdict is Benign. Variant got -11 ACMG points: 0P and 11B. BP4_ModerateBP6BA1

The NM_001370959.1(POU6F2):c.1114-7C>T variant causes a splice region, intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.265 in 1,612,578 control chromosomes in the GnomAD database, including 58,903 homozygotes. In-silico tool predicts a benign outcome for this variant. 3/3 splice prediction tools predict no significant impact on normal splicing. Variant has been reported in ClinVar as Benign (no stars).

Frequency

Genomes: 𝑓 0.29 ( 6635 hom., cov: 31)

Exomes 𝑓: 0.26 ( 52268 hom. )

Consequence

POU6F2
NM_001370959.1 splice_region, intron

Scores

Splicing: ADA: 0.001079

Clinical Significance

Benign no assertion criteria provided B:1

Conservation

PhyloP100: 0.476

Variant links:

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 links:

LOC105375238 (HGNC:):

LOC105375238 links:

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ACMG classification

Classification made for transcript

Verdict is Benign. Variant got -11 ACMG points.

BP4

Computational evidence support a benign effect (BayesDel_noAF=-0.3).

BP6

Variant 7-39433070-C-T is Benign according to our data. Variant chr7-39433070-C-T is described in ClinVar as [Benign]. Clinvar id is 3060258.Status of the report is no_assertion_criteria_provided, 0 stars.

BA1

GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.496 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
POU6F2	NM_001370959.1 link	c.1114-7C>T		splice_region_variant, intron_variant	Intron 6 of 9	ENST00000518318.7	NP_001357888.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
POU6F2	ENST00000518318.7 link	c.1114-7C>T		splice_region_variant, intron_variant	Intron 6 of 9	1	NM_001370959.1	ENSP00000430514.3		A0A6E1XZL4

Frequencies

GnomAD3 genomes

AF:

0.288

AC:

43596

AN:

151598

Hom.:

6625

Cov.:

show subpopulations

Gnomad AFR

AF:

0.339

Gnomad AMI

AF:

0.0998

Gnomad AMR

AF:

0.287

Gnomad ASJ

AF:

0.283

Gnomad EAS

AF:

0.512

Gnomad SAS

AF:

0.220

Gnomad FIN

AF:

0.268

Gnomad MID

AF:

0.248

Gnomad NFE

AF:

0.251

Gnomad OTH

AF:

0.289

GnomAD3 exomes

AF:

0.284

AC:

70791

AN:

249264

Hom.:

10664

AF XY:

0.277

AC XY:

37292

AN XY:

134818

show subpopulations

Gnomad AFR exome

AF:

0.331

Gnomad AMR exome

AF:

0.310

Gnomad ASJ exome

AF:

0.286

Gnomad EAS exome

AF:

0.515

Gnomad SAS exome

AF:

0.214

Gnomad FIN exome

AF:

0.270

Gnomad NFE exome

AF:

0.254

Gnomad OTH exome

AF:

0.278

GnomAD4 exome

AF:

0.263

AC:

384374

AN:

1460862

Hom.:

52268

Cov.:

AF XY:

0.261

AC XY:

189473

AN XY:

726724

show subpopulations

Gnomad4 AFR exome

AF:

0.335

Gnomad4 AMR exome

AF:

0.310

Gnomad4 ASJ exome

AF:

0.288

Gnomad4 EAS exome

AF:

0.492

Gnomad4 SAS exome

AF:

0.217

Gnomad4 FIN exome

AF:

0.273

Gnomad4 NFE exome

AF:

0.253

Gnomad4 OTH exome

AF:

0.276

GnomAD4 genome

AF:

0.288

AC:

43637

AN:

151716

Hom.:

6635

Cov.:

AF XY:

0.289

AC XY:

21394

AN XY:

74116

show subpopulations

Gnomad4 AFR

AF:

0.339

Gnomad4 AMR

AF:

0.287

Gnomad4 ASJ

AF:

0.283

Gnomad4 EAS

AF:

0.512

Gnomad4 SAS

AF:

0.220

Gnomad4 FIN

AF:

0.268

Gnomad4 NFE

AF:

0.251

Gnomad4 OTH

AF:

0.285

Alfa

AF:

0.268

Hom.:

3703

Bravo

AF:

0.296

Asia WGS

AF:

0.367

AC:

1274

AN:

3478

EpiCase

AF:

0.250

EpiControl

AF:

0.246

ClinVar

Significance: Benign

Submissions summary: Benign:1

Revision: no assertion criteria provided

LINK: link

Submissions by phenotype

POU6F2-related disorder

Benign:1

Oct 21, 2019

PreventionGenetics, part of Exact Sciences

Significance: Benign

Review Status: no assertion criteria provided

Collection Method: clinical testing

This variant is classified as benign based on ACMG/AMP sequence variant interpretation guidelines (Richards et al. 2015 PMID: 25741868, with internal and published modifications). -

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

BayesDel_noAF

Benign

-0.30

CADD

Benign

DANN

Benign

0.82

Splicing

Name

Calibrated prediction

Score

Prediction

dbscSNV1_ADA

Benign

0.0011

dbscSNV1_RF

Benign

0.016

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

Publications

LitVar

Below is the list of publications found by LitVar. It may be empty.

Variant summary

Frequency

Consequence

Scores

Clinical Significance

Conservation

ACMG classification

Transcripts

RefSeq

Ensembl

Frequencies

ClinVar

Submissions by phenotype

Computational scores

Splicing

Publications

LitVar

Other links and lift over