Variant chr19-17236044-G-A details in Genebe, Genetics Data Aggregator

Variant summary

Our verdict is Benign. Variant got -8 ACMG points: 0P and 8B. BP4_StrongBS2

The NM_005234.4(NR2F6):c.395C>T(p.Pro132Leu) variant causes a missense change. The variant allele was found at a frequency of 0.0000962 in 1,350,996 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Uncertain significance (★).

Frequency

Genomes: 𝑓 0.00012 ( 0 hom., cov: 29)

Exomes 𝑓: 0.000093 ( 0 hom. )

Consequence

NR2F6
NM_005234.4 missense

Scores

Clinical Significance

Uncertain significance criteria provided, single submitter U:1

Conservation

PhyloP100: 6.66

Variant links:

Genes affected

NR2F6 (HGNC:7977): (nuclear receptor subfamily 2 group F member 6) Enables DNA-binding transcription factor activity and sequence-specific double-stranded DNA binding activity. Involved in negative regulation of transcription by RNA polymerase II. Located in nucleus. [provided by Alliance of Genome Resources, Apr 2022]

NR2F6 links:

Genome browser will be placed here

ACMG classification

Classification made for transcript

Verdict is Benign. Variant got -8 ACMG points.

BP4

Computational evidence support a benign effect (MetaRNN=0.005493015).

BS2

High AC in GnomAd4 at 18 AD gene.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
NR2F6	NM_005234.4 linkuse as main transcript	c.395C>T	p.Pro132Leu	missense_variant	3/4	ENST00000291442.4

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
NR2F6	ENST00000291442.4 linkuse as main transcript	c.395C>T	p.Pro132Leu	missense_variant	3/4	1	NM_005234.4	P1
NR2F6	ENST00000596878.1 linkuse as main transcript	c.35C>T	p.Pro12Leu	missense_variant	3/3	3

Frequencies

GnomAD3 genomes

AF:

0.000123

AC:

AN:

146376

Hom.:

Cov.:

show subpopulations

Gnomad AFR

AF:

0.000404

Gnomad AMI

AF:

0.00

Gnomad AMR

AF:

0.0000679

Gnomad ASJ

AF:

0.00

Gnomad EAS

AF:

0.00

Gnomad SAS

AF:

0.00

Gnomad FIN

AF:

0.00

Gnomad MID

AF:

0.00

Gnomad NFE

AF:

0.0000151

Gnomad OTH

AF:

0.00

GnomAD3 exomes

AF:

0.000222

AC:

AN:

13510

Hom.:

AF XY:

0.000240

AC XY:

AN XY:

8332

show subpopulations

Gnomad AFR exome

AF:

0.00350

Gnomad AMR exome

AF:

0.00

Gnomad ASJ exome

AF:

0.00

Gnomad EAS exome

AF:

0.00

Gnomad SAS exome

AF:

0.00

Gnomad FIN exome

AF:

0.00

Gnomad NFE exome

AF:

0.000361

Gnomad OTH exome

AF:

0.00

GnomAD4 exome

AF:

0.0000930

AC:

112

AN:

1204518

Hom.:

Cov.:

AF XY:

0.0000920

AC XY:

AN XY:

587138

show subpopulations

Gnomad4 AFR exome

AF:

0.000418

Gnomad4 AMR exome

AF:

0.00

Gnomad4 ASJ exome

AF:

0.00

Gnomad4 EAS exome

AF:

0.00

Gnomad4 SAS exome

AF:

0.00

Gnomad4 FIN exome

AF:

0.00

Gnomad4 NFE exome

AF:

0.0000956

Gnomad4 OTH exome

AF:

0.000142

GnomAD4 genome

AF:

0.000123

AC:

AN:

146478

Hom.:

Cov.:

AF XY:

0.000154

AC XY:

AN XY:

71462

show subpopulations

Gnomad4 AFR

AF:

0.000403

Gnomad4 AMR

AF:

0.0000678

Gnomad4 ASJ

AF:

0.00

Gnomad4 EAS

AF:

0.00

Gnomad4 SAS

AF:

0.00

Gnomad4 FIN

AF:

0.00

Gnomad4 NFE

AF:

0.0000151

Gnomad4 OTH

AF:

0.00

Alfa

AF:

0.0000712

Hom.:

Bravo

AF:

0.000223

ExAC

AF:

0.0000873

AC:

ClinVar

Significance: Uncertain significance

Submissions summary: Uncertain:1

Revision: criteria provided, single submitter

LINK: link

Submissions by phenotype

not specified

Uncertain:1

Uncertain significance, criteria provided, single submitter

clinical testing

Ambry Genetics

Dec 31, 2023

The c.395C>T (p.P132L) alteration is located in exon 3 (coding exon 3) of the NR2F6 gene. This alteration results from a C to T substitution at nucleotide position 395, causing the proline (P) at amino acid position 132 to be replaced by a leucine (L). Based on insufficient or conflicting evidence, the clinical significance of this alteration remains unclear. -

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

AlphaMissense

Uncertain

0.51

BayesDel_addAF

Benign

-0.012

BayesDel_noAF

Benign

-0.25

CADD

Uncertain

DANN

Uncertain

1.0

DEOGEN2

Uncertain

0.60

D;.;.

Eigen

Uncertain

0.20

Eigen_PC

Benign

0.19

FATHMM_MKL

Benign

0.76

LIST_S2

Uncertain

0.92

D;D;T

MetaRNN

Benign

0.0055

T;T;T

MetaSVM

Benign

-0.81

MutationAssessor

Benign

1.6

L;.;.

MutationTaster

Benign

1.0

PrimateAI

Pathogenic

0.84

PROVEAN

Pathogenic

-6.6

D;.;.

REVEL

Benign

0.26

Sift

Uncertain

0.0010

D;.;.

Sift4G

Uncertain

0.0030

D;.;.

Polyphen

0.90

P;.;.

Vest4

0.44

MutPred

0.34

Loss of disorder (P = 0.0212);.;.;

MVP

0.51

MPC

2.2

ClinPred

0.28

GERP RS

3.6

RBP_binding_hub_radar

0.92

RBP_regulation_power_radar

2.6

Varity_R

0.63

gMVP

0.66

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

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