dbSNP rs104894492: NR2E3:p.Arg76Arg (chr15-71811590-C-A) – ACMG Classification: Likely_benign (-3 pts)

Variant summary

Our verdict is Likely benign. The variant received -3 ACMG points: 2P and 5B. PM2BP4_ModerateBP6_ModerateBP7

The NM_014249.4(NR2E3):c.226C>A(p.Arg76Arg) variant causes a synonymous change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00000276 in 1,451,636 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: not found (cov: 33)

Exomes 𝑓: 0.0000028 ( 0 hom. )

Consequence

NR2E3
NM_014249.4 synonymous

Scores

Clinical Significance

Likely benign criteria provided, single submitter B:1

Conservation

PhyloP100: -0.526

Publications

14 publications found

Variant links:

Genes affected

NR2E3 (HGNC:7974): (nuclear receptor subfamily 2 group E member 3) This protein is part of a large family of nuclear receptor transcription factors involved in signaling pathways. Nuclear receptors have been shown to regulate pathways involved in embryonic development, as well as in maintenance of proper cell function in adults. Members of this family are characterized by discrete domains that function in DNA and ligand binding. This gene encodes a retinal nuclear receptor that is a ligand-dependent transcription factor. Defects in this gene are a cause of enhanced S cone syndrome. Alternatively spliced transcript variants encoding different isoforms have been identified. [provided by RefSeq, Jul 2008]

NR2E3 Gene-Disease associations (from GenCC):

retinitis pigmentosa 37
Inheritance: AD, AR Classification: DEFINITIVE, STRONG, LIMITED Submitted by: G2P, Labcorp Genetics (formerly Invitae)
enhanced S-cone syndrome
Inheritance: AR Classification: DEFINITIVE, STRONG Submitted by: Labcorp Genetics (formerly Invitae), G2P, Laboratory for Molecular Medicine
retinitis pigmentosa
Inheritance: AD Classification: SUPPORTIVE Submitted by: Orphanet
Goldmann-Favre syndrome
Inheritance: AR Classification: SUPPORTIVE Submitted by: Orphanet

NR2E3 links:

Genome browser will be placed here

ACMG classification

Classification was made for transcript

Our verdict: Likely_benign. The variant received -3 ACMG points.

PM2

Very rare variant in population databases, with high coverage;

BP4

Computational evidence support a benign effect (BayesDel_noAF=-0.4).

BP6

Variant 15-71811590-C-A is Benign according to our data. Variant chr15-71811590-C-A is described in ClinVar as Likely_benign. ClinVar VariationId is 967420.Status of the report is criteria_provided_single_submitter, 1 stars.

BP7

Synonymous conserved (PhyloP=-0.526 with no splicing effect.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
NR2E3	NM_014249.4 link	c.226C>A	p.Arg76Arg	synonymous_variant	Exon 2 of 8	ENST00000617575.5	NP_055064.1
NR2E3	NM_016346.4 link	c.226C>A	p.Arg76Arg	synonymous_variant	Exon 2 of 7		NP_057430.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein
NR2E3	ENST00000617575.5 link	c.226C>A	p.Arg76Arg	synonymous_variant	Exon 2 of 8	1	NM_014249.4	ENSP00000482504.1
NR2E3	ENST00000621098.1 link	c.226C>A	p.Arg76Arg	synonymous_variant	Exon 2 of 7	1		ENSP00000479962.1
NR2E3	ENST00000621736.4 link	c.-39C>A		5_prime_UTR_variant	Exon 4 of 10	2		ENSP00000479254.1

Frequencies

GnomAD3 genomes

Cov.:

GnomAD2 exomes

AF:

0.0000131

AC:

AN:

229784

AF XY:

0.0000240

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 FIN exome

AF:

0.00

Gnomad NFE exome

AF:

0.0000289

Gnomad OTH exome

AF:

0.00

GnomAD4 exome

AF:

0.00000276

AC:

AN:

1451636

Hom.:

Cov.:

AF XY:

0.00000555

AC XY:

AN XY:

721098

show subpopulations

African (AFR)

AF:

0.00

AC:

AN:

33328

American (AMR)

AF:

0.00

AC:

AN:

43142

Ashkenazi Jewish (ASJ)

AF:

0.00

AC:

AN:

25954

East Asian (EAS)

AF:

0.00

AC:

AN:

39190

South Asian (SAS)

AF:

0.00

AC:

AN:

84126

European-Finnish (FIN)

AF:

0.00

AC:

AN:

52338

Middle Eastern (MID)

AF:

0.00

AC:

AN:

5722

European-Non Finnish (NFE)

AF:

0.00000271

AC:

AN:

1107858

Other (OTH)

AF:

0.0000167

AC:

AN:

59978

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.500

Heterozygous variant carriers

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

GnomAD4 genome

Cov.:

ClinVar

Significance: Likely benign

Submissions summary: Benign:1

Revision: criteria provided, single submitter

LINK: link

Submissions by phenotype

not provided

Benign:1

Oct 21, 2024

Labcorp Genetics (formerly Invitae), Labcorp

Significance:Likely benign

Review Status:criteria provided, single submitter

Collection Method:clinical testing

- -

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

BayesDel_noAF

Benign

-0.40

CADD

Benign

4.2

(source)

DANN

Benign

0.83

PhyloP100

-0.53

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

You must be logged in to view publications. This limit was set because tens of millions (!) of queries from AI bots are generated daily.

Variant summary

Frequency

Consequence

Scores

Clinical Significance

Conservation

Publications

ACMG classification

Transcripts

RefSeq

Ensembl

Frequencies

ClinVar

Submissions by phenotype

Computational scores

Splicing

Publications

Other links and lift over