rs11632611

Variant names:

• chr15-71803372-G-A
• rs11632611
• ENST00000621736.4:c.-403-3646G>A

Variant summary

Our verdict is Benign. The variant received -12 ACMG points: 0P and 12B. BP4_Strong BA1

The ENST00000621736.4(NR2E3):​c.-403-3646G>A variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.515 in 151,842 control chromosomes in the GnomAD database, including 23,570 homozygotes. In-silico tool predicts a benign outcome for this variant. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar.

• Frequency: Genomes: 𝑓 0.52 (23570 hom., cov: 32)
• Consequence: NR2E3 ENST00000621736.4 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 1.42
• Publications: 4 publications found

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

ACMG classification

Our verdict: Benign. The variant received -12 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.87).
• BA1: GnomAd4 highest subpopulation (NFE) allele frequency at 95% confidence interval = 0.654 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
NR2E3	ENST00000621736.4	c.-403-3646G>A		intron_variant	Intron 1 of 9	2		ENSP00000479254.1

Frequencies

GnomAD3 genomes AF: 0.516 AC: 78227 AN: 151726 Hom.: 23573 Cov.: 32

Gnomad AFR AF: 0.200

Gnomad AMI AF: 0.548

Gnomad AMR AF: 0.625

Gnomad ASJ AF: 0.650

Gnomad EAS AF: 0.242

Gnomad SAS AF: 0.611

Gnomad FIN AF: 0.699

Gnomad MID AF: 0.668

Gnomad NFE AF: 0.659

Gnomad OTH AF: 0.549

We have no GnomAD4 exomes data on this position. Probably position not covered by the project.

GnomAD4 genome AF: 0.515 AC: 78227 AN: 151842 Hom.: 23570 Cov.: 32 AF XY: 0.520 AC XY: 38580 AN XY: 74206

African (AFR) AF: 0.200 AC: 8267 AN: 41354

American (AMR) AF: 0.625 AC: 9549 AN: 15278

Ashkenazi Jewish (ASJ) AF: 0.650 AC: 2254 AN: 3468

East Asian (EAS) AF: 0.242 AC: 1252 AN: 5166

South Asian (SAS) AF: 0.611 AC: 2941 AN: 4810

European-Finnish (FIN) AF: 0.699 AC: 7369 AN: 10538

Middle Eastern (MID) AF: 0.660 AC: 194 AN: 294

European-Non Finnish (NFE) AF: 0.659 AC: 44759 AN: 67916

Other (OTH) AF: 0.542 AC: 1142 AN: 2106

Alfa AF: 0.630 Hom.: 48066

Bravo AF: 0.493

Asia WGS AF: 0.360 AC: 1253 AN: 3476

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.87
CADD	Benign	3.8
DANN	Benign	0.50
PhyloP100		1.4

Splicing

Find out detailed SpliceAI scores and Pangolin per-transcript scores at spliceailookup.broadinstitute.org

Other links and lift over

dbSNP: rs11632611; hg19: chr15-72095711;