Variant 19-17235954-G-A details in Genebe, Genetics Data Aggregator

Variant summary

Our verdict is Likely benign. Variant got -5 ACMG points: 0P and 5B. BP4BS2

The NM_005234.4(NR2F6):c.485C>T(p.Pro162Leu) variant causes a missense change. The variant allele was found at a frequency of 0.0000872 in 1,479,288 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a benign outcome for this variant. 13/21 in silico tools predict a benign outcome for this variant. Variant has been reported in ClinVar as Uncertain significance (★).

Frequency

Genomes: 𝑓 0.000033 ( 0 hom., cov: 31)

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: 3.97

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:

ENSG00000269095 (HGNC:):

ENSG00000269095 links:

Genome browser will be placed here

ACMG classification

Classification made for transcript

Verdict is Likely_benign. Variant got -5 ACMG points.

BP4

Computational evidence support a benign effect (MetaRNN=0.37177974).

BS2

High AC in GnomAd4 at 5 AD gene.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
NR2F6	NM_005234.4 link	c.485C>T	p.Pro162Leu	missense_variant	3/4	ENST00000291442.4	NP_005225.2	P10588F1D8R3

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	UniProt
NR2F6	ENST00000291442.4 link	c.485C>T	p.Pro162Leu	missense_variant	3/4	1	NM_005234.4	ENSP00000291442.2	P10588
ENSG00000269095	ENST00000594059.1 link	c.125C>T	p.Pro42Leu	missense_variant	5/5	4		ENSP00000473056.1	M0R384
NR2F6	ENST00000596878.1 link	c.125C>T	p.Pro42Leu	missense_variant	3/3	3		ENSP00000471686.1	M0R175

Frequencies

GnomAD3 genomes

AF:

0.0000331

AC:

AN:

151144

Hom.:

Cov.:

show subpopulations

Gnomad AFR

AF:

0.0000243

Gnomad AMI

AF:

0.00

Gnomad AMR

AF:

0.00

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:

0.0000591

Gnomad OTH

AF:

0.00

GnomAD3 exomes

AF:

0.0000338

AC:

AN:

88706

Hom.:

AF XY:

0.0000199

AC XY:

AN XY:

50316

show subpopulations

Gnomad AFR exome

AF:

0.00

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:

0.0000906

Gnomad OTH exome

AF:

0.00

GnomAD4 exome

AF:

0.0000934

AC:

124

AN:

1328144

Hom.:

Cov.:

AF XY:

0.0000946

AC XY:

AN XY:

655358

show subpopulations

Gnomad4 AFR exome

AF:

0.00

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:

0.000117

Gnomad4 OTH exome

AF:

0.0000181

GnomAD4 genome

AF:

0.0000331

AC:

AN:

151144

Hom.:

Cov.:

AF XY:

0.00

AC XY:

AN XY:

73846

show subpopulations

Gnomad4 AFR

AF:

0.0000243

Gnomad4 AMR

AF:

0.00

Gnomad4 ASJ

AF:

0.00

Gnomad4 EAS

AF:

0.00

Gnomad4 SAS

AF:

0.00

Gnomad4 FIN

AF:

0.00

Gnomad4 NFE

AF:

0.0000591

Gnomad4 OTH

AF:

0.00

Alfa

AF:

0.0000712

Hom.:

Bravo

AF:

0.0000416

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

Sep 02, 2024

The c.485C>T (p.P162L) 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 485, causing the proline (P) at amino acid position 162 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

Benign

0.14

BayesDel_addAF

Benign

0.0064

BayesDel_noAF

Benign

-0.23

CADD

Benign

DANN

Benign

0.92

DEOGEN2

Benign

0.13

T;.;.

Eigen

Benign

-0.37

Eigen_PC

Benign

-0.27

FATHMM_MKL

Benign

0.65

LIST_S2

Uncertain

0.92

D;D;T

M_CAP

Pathogenic

0.99

MetaRNN

Benign

0.37

T;T;T

MetaSVM

Benign

-0.28

MutationAssessor

Benign

0.69

N;.;.

PrimateAI

Pathogenic

0.92

PROVEAN

Benign

0.74

N;.;.

REVEL

Benign

0.26

Sift

Benign

0.42

T;.;.

Sift4G

Benign

0.41

T;.;.

Polyphen

0.12

B;.;.

Vest4

0.15

MutPred

0.51

Gain of catalytic residue at P162 (P = 0.0329);.;.;

MVP

0.74

MPC

1.4

ClinPred

0.11

GERP RS

2.5

RBP_binding_hub_radar

0.0

RBP_regulation_power_radar

2.1

Varity_R

0.045

gMVP

0.33

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