rs11632611

chr15-71803372-G-A

Variant summary

Our verdict is Benign. Variant got -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

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]

ACMG classification

Verdict is Benign. Variant got -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/exons	MANE	UniProt

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
NR2E3	ENST00000621736.4	c.-403-3646G>A		intron_variant		2

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

Gnomad4 AFR AF: 0.200

Gnomad4 AMR AF: 0.625

Gnomad4 ASJ AF: 0.650

Gnomad4 EAS AF: 0.242

Gnomad4 SAS AF: 0.611

Gnomad4 FIN AF: 0.699

Gnomad4 NFE AF: 0.659

Gnomad4 OTH AF: 0.542

Alfa AF: 0.636 Hom.: 40568

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

Splicing

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

Publications

LitVar

Other links and lift over

dbSNP: rs11632611; hg19: chr15-72095711;