Variant rs143951395 details in Genebe, Genetics Data Aggregator

Variant summary

Our verdict is Benign. Variant got -19 ACMG points: 0P and 19B. BP4_ModerateBP6_Very_StrongBP7BS1BS2

The NM_021005.4(NR2F2):c.537C>T(p.Ser179=) variant causes a synonymous change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0000997 in 1,614,148 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 Likely benign (★★).

Frequency

Genomes: 𝑓 0.00051 ( 0 hom., cov: 33)

Exomes 𝑓: 0.000057 ( 0 hom. )

Consequence

NR2F2
NM_021005.4 synonymous

Scores

Clinical Significance

Benign/Likely benign criteria provided, multiple submitters, no conflicts B:2

Conservation

PhyloP100: 0.977

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:

Genome browser will be placed here

ACMG classification

Classification made for transcript

Verdict is Benign. Variant got -19 ACMG points.

BP4

Computational evidence support a benign effect (BayesDel_noAF=-0.36).

BP6

Variant 15-96334170-C-T is Benign according to our data. Variant chr15-96334170-C-T is described in ClinVar as [Likely_benign]. Clinvar id is 477848.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars.

BP7

Synonymous conserved (PhyloP=0.977 with no splicing effect.

BS1

Variant frequency is greater than expected in population afr. gnomad4 allele frequency = 0.000512 (78/152376) while in subpopulation AFR AF= 0.00173 (72/41596). AF 95% confidence interval is 0.00141. There are 0 homozygotes in gnomad4. There are 31 alleles in male gnomad4 subpopulation. This position pass quality control queck.

BS2

High AC in GnomAd at 76 AD gene.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE
NR2F2	NM_021005.4 linkuse as main transcript	c.537C>T	p.Ser179=	synonymous_variant	2/3	ENST00000394166.8
NR2F2	NM_001145155.2 linkuse as main transcript	c.138C>T	p.Ser46=	synonymous_variant	2/3
NR2F2	NM_001145156.1 linkuse as main transcript	c.78C>T	p.Ser26=	synonymous_variant	2/3
NR2F2	NM_001145157.2 linkuse as main transcript	c.78C>T	p.Ser26=	synonymous_variant	2/3

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
NR2F2	ENST00000394166.8 linkuse as main transcript	c.537C>T	p.Ser179=	synonymous_variant	2/3	1	NM_021005.4	P1	P24468-1

Frequencies

GnomAD3 genomes

AF:

0.000499

AC:

AN:

152258

Hom.:

Cov.:

show subpopulations

Gnomad AFR

AF:

0.00169

Gnomad AMI

AF:

0.00

Gnomad AMR

AF:

0.000262

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:

0.00

Gnomad OTH

AF:

0.000955

GnomAD3 exomes

AF:

0.000123

AC:

AN:

251340

Hom.:

AF XY:

0.0000957

AC XY:

AN XY:

135882

show subpopulations

Gnomad AFR exome

AF:

0.00191

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:

0.00

Gnomad OTH exome

AF:

0.00

GnomAD4 exome

AF:

0.0000568

AC:

AN:

1461772

Hom.:

Cov.:

AF XY:

0.0000454

AC XY:

AN XY:

727200

show subpopulations

Gnomad4 AFR exome

AF:

0.00206

Gnomad4 AMR exome

AF:

0.00

Gnomad4 ASJ exome

AF:

0.00

Gnomad4 EAS exome

AF:

0.00

Gnomad4 SAS exome

AF:

0.0000116

Gnomad4 FIN exome

AF:

0.00

Gnomad4 NFE exome

AF:

8.99e-7

Gnomad4 OTH exome

AF:

0.000149

GnomAD4 genome

AF:

0.000512

AC:

AN:

152376

Hom.:

Cov.:

AF XY:

0.000416

AC XY:

AN XY:

74516

show subpopulations

Gnomad4 AFR

AF:

0.00173

Gnomad4 AMR

AF:

0.000261

Gnomad4 ASJ

AF:

0.00

Gnomad4 EAS

AF:

0.00

Gnomad4 SAS

AF:

0.00

Gnomad4 FIN

AF:

0.00

Gnomad4 NFE

AF:

0.00

Gnomad4 OTH

AF:

0.000945

Alfa

AF:

0.000409

Hom.:

Bravo

AF:

0.000695

ClinVar

Significance: Benign/Likely benign

Submissions summary: Benign:2

Revision: criteria provided, multiple submitters, no conflicts

LINK: link

Submissions by phenotype

Congenital heart defects, multiple types, 4;C5394441:46,xx sex reversal 5

Benign:1

Likely benign, criteria provided, single submitter

clinical testing

Fulgent Genetics, Fulgent Genetics

Mar 29, 2022

- -

Congenital heart defects, multiple types, 4

Benign:1

Benign, criteria provided, single submitter

clinical testing

Invitae

Sep 01, 2022

- -

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

BayesDel_noAF

Benign

-0.36

Cadd

Benign

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