Variant rs199886454 details in Genebe, Genetics Data Aggregator

Variant summary

Our verdict is Benign. Variant got -21 ACMG points: 0P and 21B. BP4_StrongBP6_Very_StrongBP7BS1BS2

The NM_021005.4(NR2F2):c.834G>A(p.Ser278=) variant causes a synonymous change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.000713 in 1,613,970 control chromosomes in the GnomAD database, including 12 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★★).

Frequency

Genomes: 𝑓 0.00068 ( 1 hom., cov: 33)

Exomes 𝑓: 0.00072 ( 11 hom. )

Consequence

NR2F2
NM_021005.4 synonymous

Scores

Clinical Significance

Benign criteria provided, multiple submitters, no conflicts B:2

Conservation

PhyloP100: 0.419

Variant links:

Genes affected

NR2F2 (HGNC:7976): (nuclear receptor subfamily 2 group F member 2) This gene encodes a member of the steroid thyroid hormone superfamily of nuclear receptors. The encoded protein is a ligand inducible transcription factor that is involved in the regulation of many different genes. Alternate splicing results in multiple transcript variants. [provided by RefSeq, Mar 2010]

NR2F2 links:

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ACMG classification

Classification made for transcript

Verdict is Benign. Variant got -21 ACMG points.

BP4

Computational evidence support a benign effect (BayesDel_noAF=-0.48).

BP6

Variant 15-96334467-G-A is Benign according to our data. Variant chr15-96334467-G-A is described in ClinVar as [Benign]. Clinvar id is 413760.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars.

BP7

Synonymous conserved (PhyloP=0.419 with no splicing effect.

BS1

Variant frequency is greater than expected in population sas. gnomad4 allele frequency = 0.000676 (103/152324) while in subpopulation SAS AF= 0.0143 (69/4826). AF 95% confidence interval is 0.0116. There are 1 homozygotes in gnomad4. There are 66 alleles in male gnomad4 subpopulation. Median coverage is 33. This position pass quality control queck.

BS2

High AC in GnomAd4 at 103 AD gene.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE
NR2F2	NM_021005.4 linkuse as main transcript	c.834G>A	p.Ser278=	synonymous_variant	2/3	ENST00000394166.8
NR2F2	NM_001145155.2 linkuse as main transcript	c.435G>A	p.Ser145=	synonymous_variant	2/3
NR2F2	NM_001145156.1 linkuse as main transcript	c.375G>A	p.Ser125=	synonymous_variant	2/3
NR2F2	NM_001145157.2 linkuse as main transcript	c.375G>A	p.Ser125=	synonymous_variant	2/3

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
NR2F2	ENST00000394166.8 linkuse as main transcript	c.834G>A	p.Ser278=	synonymous_variant	2/3	1	NM_021005.4	P1	P24468-1
NR2F2	ENST00000421109.6 linkuse as main transcript	c.435G>A	p.Ser145=	synonymous_variant	2/3	1			P24468-2
NR2F2	ENST00000453270.2 linkuse as main transcript	c.375G>A	p.Ser125=	synonymous_variant	2/3	1			P24468-3
NR2F2	ENST00000394171.6 linkuse as main transcript	c.375G>A	p.Ser125=	synonymous_variant	2/3	2			P24468-3

Frequencies

GnomAD3 genomes

AF:

0.000683

AC:

104

AN:

152206

Hom.:

Cov.:

show subpopulations

Gnomad AFR

AF:

0.0000965

Gnomad AMI

AF:

0.00

Gnomad AMR

AF:

0.00144

Gnomad ASJ

AF:

0.00

Gnomad EAS

AF:

0.00

Gnomad SAS

AF:

0.0145

Gnomad FIN

AF:

0.0000941

Gnomad MID

AF:

0.00

Gnomad NFE

AF:

0.0000294

Gnomad OTH

AF:

0.00239

GnomAD3 exomes

AF:

0.00147

AC:

368

AN:

250724

Hom.:

AF XY:

0.00204

AC XY:

277

AN XY:

135694

show subpopulations

Gnomad AFR exome

AF:

0.00

Gnomad AMR exome

AF:

0.000116

Gnomad ASJ exome

AF:

0.00

Gnomad EAS exome

AF:

0.0000544

Gnomad SAS exome

AF:

0.0112

Gnomad FIN exome

AF:

0.0000462

Gnomad NFE exome

AF:

0.0000883

Gnomad OTH exome

AF:

0.00131

GnomAD4 exome

AF:

0.000717

AC:

1048

AN:

1461646

Hom.:

Cov.:

AF XY:

0.00103

AC XY:

750

AN XY:

727134

show subpopulations

Gnomad4 AFR exome

AF:

0.0000597

Gnomad4 AMR exome

AF:

0.000268

Gnomad4 ASJ exome

AF:

0.00

Gnomad4 EAS exome

AF:

0.0000252

Gnomad4 SAS exome

AF:

0.0105

Gnomad4 FIN exome

AF:

0.0000563

Gnomad4 NFE exome

AF:

0.0000522

Gnomad4 OTH exome

AF:

0.00101

GnomAD4 genome

AF:

0.000676

AC:

103

AN:

152324

Hom.:

Cov.:

AF XY:

0.000886

AC XY:

AN XY:

74482

show subpopulations

Gnomad4 AFR

AF:

0.0000962

Gnomad4 AMR

AF:

0.00144

Gnomad4 ASJ

AF:

0.00

Gnomad4 EAS

AF:

0.00

Gnomad4 SAS

AF:

0.0143

Gnomad4 FIN

AF:

0.0000941

Gnomad4 NFE

AF:

0.0000294

Gnomad4 OTH

AF:

0.00237

Alfa

AF:

0.000115

Hom.:

Bravo

AF:

0.000438

Asia WGS

AF:

0.00433

AC:

AN:

3478

EpiCase

AF:

0.0000545

EpiControl

AF:

0.000296

ClinVar

Significance: Benign

Submissions summary: Benign:2

Revision: criteria provided, multiple submitters, no conflicts

LINK: link

Submissions by phenotype

Congenital heart defects, multiple types, 4

Benign:1

Benign, criteria provided, single submitter

clinical testing

Invitae

Nov 28, 2022

- -

not provided

Benign:1

Benign, criteria provided, single submitter

clinical testing

CeGaT Center for Human Genetics Tuebingen

Oct 01, 2022

NR2F2: BS1, BS2 -

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

BayesDel_noAF

Benign

-0.48

CADD

Benign

8.6

DANN

Benign

0.94

RBP_binding_hub_radar

0.0

RBP_regulation_power_radar

1.7

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