Variant 15-71811455-T-C details in Genebe, Genetics Data Aggregator

Variant summary

Our verdict is Benign. Variant got -20 ACMG points: 0P and 20B. BP4_StrongBP6_Very_StrongBA1

The NM_014249.4(NR2E3):c.119-28T>C variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0488 in 1,502,626 control chromosomes in the GnomAD database, including 4,405 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Likely benign (★★).

Frequency

Genomes: 𝑓 0.10 ( 1303 hom., cov: 32)

Exomes 𝑓: 0.043 ( 3102 hom. )

Consequence

NR2E3
NM_014249.4 intron

Scores

Clinical Significance

Benign/Likely benign criteria provided, multiple submitters, no conflicts B:3

Conservation

PhyloP100: 0.0690

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 links:

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ACMG classification

Classification made for transcript

Verdict is Benign. Variant got -20 ACMG points.

BP4

Computational evidence support a benign effect (BayesDel_noAF=-0.88).

BP6

Variant 15-71811455-T-C is Benign according to our data. Variant chr15-71811455-T-C is described in ClinVar as [Likely_benign]. Clinvar id is 260366.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars. Variant chr15-71811455-T-C is described in Lovd as [Benign].

BA1

GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.25 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
NR2E3	NM_014249.4 linkuse as main transcript	c.119-28T>C		intron_variant		ENST00000617575.5	NP_055064.1
NR2E3	NM_016346.4 linkuse as main transcript	c.119-28T>C		intron_variant			NP_057430.1

Ensembl

Gene	Transcript	HGVSc	Effect	TSL	MANE	Protein	Appris	UniProt
NR2E3	ENST00000617575.5 linkuse as main transcript	c.119-28T>C	intron_variant	1	NM_014249.4	ENSP00000482504	P1	Q9Y5X4-1
NR2E3	ENST00000621098.1 linkuse as main transcript	c.119-28T>C	intron_variant	1		ENSP00000479962		Q9Y5X4-2
NR2E3	ENST00000621736.4 linkuse as main transcript	c.-146-28T>C	intron_variant	2		ENSP00000479254

Frequencies

GnomAD3 genomes

AF:

0.104

AC:

14838

AN:

143252

Hom.:

1297

Cov.:

show subpopulations

Gnomad AFR

AF:

0.254

Gnomad AMI

AF:

0.0443

Gnomad AMR

AF:

0.109

Gnomad ASJ

AF:

0.0184

Gnomad EAS

AF:

0.205

Gnomad SAS

AF:

0.0692

Gnomad FIN

AF:

0.0449

Gnomad MID

AF:

0.0513

Gnomad NFE

AF:

0.0317

Gnomad OTH

AF:

0.0927

GnomAD3 exomes

AF:

0.0722

AC:

11125

AN:

154168

Hom.:

739

AF XY:

0.0671

AC XY:

5513

AN XY:

82198

show subpopulations

Gnomad AFR exome

AF:

0.217

Gnomad AMR exome

AF:

0.130

Gnomad ASJ exome

AF:

0.0198

Gnomad EAS exome

AF:

0.199

Gnomad SAS exome

AF:

0.0595

Gnomad FIN exome

AF:

0.0377

Gnomad NFE exome

AF:

0.0288

Gnomad OTH exome

AF:

0.0594

GnomAD4 exome

AF:

0.0430

AC:

58487

AN:

1359280

Hom.:

3102

Cov.:

AF XY:

0.0430

AC XY:

28870

AN XY:

670768

show subpopulations

Gnomad4 AFR exome

AF:

0.260

Gnomad4 AMR exome

AF:

0.132

Gnomad4 ASJ exome

AF:

0.0198

Gnomad4 EAS exome

AF:

0.242

Gnomad4 SAS exome

AF:

0.0579

Gnomad4 FIN exome

AF:

0.0398

Gnomad4 NFE exome

AF:

0.0267

Gnomad4 OTH exome

AF:

0.0587

GnomAD4 genome

AF:

0.104

AC:

14890

AN:

143346

Hom.:

1303

Cov.:

AF XY:

0.104

AC XY:

7256

AN XY:

69942

show subpopulations

Gnomad4 AFR

AF:

0.254

Gnomad4 AMR

AF:

0.109

Gnomad4 ASJ

AF:

0.0184

Gnomad4 EAS

AF:

0.205

Gnomad4 SAS

AF:

0.0691

Gnomad4 FIN

AF:

0.0449

Gnomad4 NFE

AF:

0.0317

Gnomad4 OTH

AF:

0.0962

Alfa

AF:

0.0195

Hom.:

ClinVar

Significance: Benign/Likely benign

Submissions summary: Benign:3

Revision: criteria provided, multiple submitters, no conflicts

LINK: link

Submissions by phenotype

not provided

Benign:2

Benign, criteria provided, single submitter	clinical testing	GeneDx	May 14, 2021	- -
Likely benign, criteria provided, single submitter	not provided	Breakthrough Genomics, Breakthrough Genomics	-	- -

not specified

Benign:1

Likely benign, criteria provided, single submitter

clinical testing

PreventionGenetics, part of Exact Sciences

- -

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

BayesDel_noAF

Benign

-0.88

CADD

Benign

1.1

DANN

Benign

0.58

Splicing

Name

Calibrated prediction

Score

Prediction

SpliceAI score (max)

0.070

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