Variant 15-71810605-G-A details in Genebe, Genetics Data Aggregator

Variant summary

Our verdict is Benign. Variant got -9 ACMG points: 0P and 9B. BP4_StrongBS1_SupportingBS2

The NM_014249.4(NR2E3):c.-139G>A variant causes a 5 prime UTR change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00722 in 1,337,828 control chromosomes in the GnomAD database, including 73 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Uncertain significance (★★).

Frequency

Genomes: 𝑓 0.0071 ( 10 hom., cov: 32)

Exomes 𝑓: 0.0072 ( 63 hom. )

Consequence

NR2E3
NM_014249.4 5_prime_UTR

Scores

Clinical Significance

Uncertain significance criteria provided, multiple submitters, no conflicts U:3

Conservation

PhyloP100: 0.981

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 -9 ACMG points.

BP4

Computational evidence support a benign effect (BayesDel_noAF=-0.85).

BS1

Variant frequency is greater than expected in population amr. gnomad4 allele frequency = 0.00708 (1078/152308) while in subpopulation AMR AF= 0.0151 (231/15310). AF 95% confidence interval is 0.0135. There are 10 homozygotes in gnomad4. There are 550 alleles in male gnomad4 subpopulation. Median coverage is 32. This position pass quality control queck. Existence of Clinvar submissions makes me limit the strength of this signal to Supporting

BS2

High Homozygotes in GnomAd4 at 10 AD,AR gene

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
NR2E3	NM_014249.4 linkuse as main transcript	c.-139G>A		5_prime_UTR_variant	1/8	ENST00000617575.5
NR2E3	NM_016346.4 linkuse as main transcript	c.-139G>A		5_prime_UTR_variant	1/7

Ensembl

Gene	Transcript	HGVSc	Effect	#exon/exons	TSL	MANE	Appris	UniProt
NR2E3	ENST00000617575.5 linkuse as main transcript	c.-139G>A	5_prime_UTR_variant	1/8	1	NM_014249.4	P1	Q9Y5X4-1
NR2E3	ENST00000621098.1 linkuse as main transcript	c.-139G>A	5_prime_UTR_variant	1/7	1			Q9Y5X4-2
NR2E3	ENST00000621736.4 linkuse as main transcript	c.-146-878G>A	intron_variant		2

Frequencies

GnomAD3 genomes

AF:

0.00709

AC:

1079

AN:

152190

Hom.:

Cov.:

show subpopulations

Gnomad AFR

AF:

0.000989

Gnomad AMI

AF:

0.00110

Gnomad AMR

AF:

0.0151

Gnomad ASJ

AF:

0.0447

Gnomad EAS

AF:

0.000193

Gnomad SAS

AF:

0.00394

Gnomad FIN

AF:

0.00207

Gnomad MID

AF:

0.0127

Gnomad NFE

AF:

0.00857

Gnomad OTH

AF:

0.0105

GnomAD4 exome

AF:

0.00724

AC:

8580

AN:

1185520

Hom.:

Cov.:

AF XY:

0.00725

AC XY:

4221

AN XY:

581910

show subpopulations

Gnomad4 AFR exome

AF:

0.00121

Gnomad4 AMR exome

AF:

0.00914

Gnomad4 ASJ exome

AF:

0.0413

Gnomad4 EAS exome

AF:

0.0000295

Gnomad4 SAS exome

AF:

0.00617

Gnomad4 FIN exome

AF:

0.00183

Gnomad4 NFE exome

AF:

0.00711

Gnomad4 OTH exome

AF:

0.00907

GnomAD4 genome

AF:

0.00708

AC:

1078

AN:

152308

Hom.:

Cov.:

AF XY:

0.00738

AC XY:

550

AN XY:

74480

show subpopulations

Gnomad4 AFR

AF:

0.000986

Gnomad4 AMR

AF:

0.0151

Gnomad4 ASJ

AF:

0.0447

Gnomad4 EAS

AF:

0.000194

Gnomad4 SAS

AF:

0.00373

Gnomad4 FIN

AF:

0.00207

Gnomad4 NFE

AF:

0.00857

Gnomad4 OTH

AF:

0.0104

Alfa

AF:

0.00174

Hom.:

Bravo

AF:

0.00769

ClinVar

Significance: Uncertain significance

Submissions summary: Uncertain:3

Revision: criteria provided, multiple submitters, no conflicts

LINK: link

Submissions by phenotype

Retinitis Pigmentosa, Recessive

Uncertain:1

Uncertain significance, criteria provided, single submitter

clinical testing

Illumina Laboratory Services, Illumina

Jun 14, 2016

- -

Enhanced S-cone syndrome

Uncertain:1

Uncertain significance, criteria provided, single submitter

clinical testing

Illumina Laboratory Services, Illumina

Jun 14, 2016

- -

not provided

Uncertain:1

Uncertain significance, criteria provided, single submitter

not provided

Breakthrough Genomics, Breakthrough Genomics

- -

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

BayesDel_noAF

Benign

-0.85

CADD

Benign

6.9

DANN

Benign

0.46

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