7-39433070-C-T

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

2
Splicing: ADA: 0.001079
2

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]

Genome browser will be placed here

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
POU6F2NM_001370959.1 linkc.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
POU6F2ENST00000518318.7 linkc.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.:
31
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.:
34
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.:
31
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
12
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.

Other links and lift over

dbSNP: rs2302125; hg19: chr7-39472669; COSMIC: COSV68873860; API