NM_014249.4:c.24G>T

Variant names:

• chr15-71810767-G-T
• rs2054171622
• NM_014249.4:c.24G>T

Variant summary

Our verdict is Likely benign. The variant received -3 ACMG points: 2P and 5B. PM2 BP4_Strong BP7

The NM_014249.4(NR2E3):​c.24G>T​(p.Leu8Leu) variant causes a synonymous change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00000141 in 1,422,616 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a benign outcome for this variant. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar. Synonymous variant affecting the same amino acid position (i.e. L8L) has been classified as Likely benign.

• Frequency:
  • Genomes: not found (cov: 32)
  • Exomes 𝑓: 0.0000014 (0 hom.)
• Consequence: NR2E3 NM_014249.4 synonymous
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -1.99
• Publications: 0 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: G2P, Labcorp Genetics (formerly Invitae), 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: 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=-0.89).
• BP7: Synonymous conserved (PhyloP=-1.99 with no splicing effect.

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_014249.4. You can select a different transcript below to see updated ACMG assignments.

RefSeq Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	NR2E3	NM_014249.4	MANE Select	c.24G>T	p.Leu8Leu	synonymous	Exon 1 of 8	NP_055064.1	Q9Y5X4-1
	NR2E3	NM_016346.4		c.24G>T	p.Leu8Leu	synonymous	Exon 1 of 7	NP_057430.1	F1D8Q9

Ensembl Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	NR2E3	ENST00000617575.5	TSL:1 MANE Select	c.24G>T	p.Leu8Leu	synonymous	Exon 1 of 8	ENSP00000482504.1	Q9Y5X4-1
	NR2E3	ENST00000621098.1	TSL:1	c.24G>T	p.Leu8Leu	synonymous	Exon 1 of 7	ENSP00000479962.1	Q9Y5X4-2
	NR2E3	ENST00000621736.4	TSL:2	c.-146-716G>T		intron	N/A	ENSP00000479254.1	Q8IVZ9

Frequencies

GnomAD3 genomes Cov.: 32

GnomAD4 exome AF: 0.00000141 AC: 2 AN: 1422616 Hom.: 0 Cov.: 31 AF XY: 0.00 AC XY: 0 AN XY: 704042

African (AFR) AF: 0.00 AC: 0 AN: 32422

American (AMR) AF: 0.00 AC: 0 AN: 38990

Ashkenazi Jewish (ASJ) AF: 0.00 AC: 0 AN: 25472

East Asian (EAS) AF: 0.00 AC: 0 AN: 37248

South Asian (SAS) AF: 0.00 AC: 0 AN: 80716

European-Finnish (FIN) AF: 0.00 AC: 0 AN: 50268

Middle Eastern (MID) AF: 0.00 AC: 0 AN: 5686

European-Non Finnish (NFE) AF: 0.00000183 AC: 2 AN: 1092834

Other (OTH) AF: 0.00 AC: 0 AN: 58980

GnomAD4 genome Cov.: 32

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.89
CADD	Benign	0.11
DANN	Benign	0.77
PhyloP100		-2.0
PromoterAI		0.023	Neutral

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

Other links and lift over

dbSNP: rs2054171622; hg19: chr15-72103107;