chr15-71811978-C-A

Variant names:

• chr15-71811978-C-A
• rs786205493
• NM_014249.4:c.373C>A

Variant summary

Our verdict is Benign. The variant received -11 ACMG points: 0P and 11B. BP4_Moderate BP6_Very_Strong BP7

The NM_014249.4(NR2E3):​c.373C>A​(p.Arg125Arg) variant causes a synonymous change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00000928 in 1,400,240 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Likely benign (★★).

• Frequency:
  • Genomes: not found (cov: 33)
  • Exomes 𝑓: 0.0000093 (0 hom.)
• Consequence: NR2E3 NM_014249.4 synonymous
• Clinical Significance: Likely benign criteria provided, multiple submitters, no conflicts B:2
• Conservation: PhyloP100: 2.56
• Publications: 7 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: Benign. The variant received -11 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.43).
• BP6: Variant 15-71811978-C-A is Benign according to our data. Variant chr15-71811978-C-A is described in ClinVar as Likely_benign. ClinVar VariationId is 2792014.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars.
• BP7: Synonymous conserved (PhyloP=2.57 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.373C>A	p.Arg125Arg	synonymous	Exon 4 of 8	NP_055064.1	Q9Y5X4-1
	NR2E3	NM_016346.4		c.373C>A	p.Arg125Arg	synonymous	Exon 4 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.373C>A	p.Arg125Arg	synonymous	Exon 4 of 8	ENSP00000482504.1	Q9Y5X4-1
	NR2E3	ENST00000621098.1	TSL:1	c.373C>A	p.Arg125Arg	synonymous	Exon 4 of 7	ENSP00000479962.1	Q9Y5X4-2
	NR2E3	ENST00000621736.4	TSL:2	c.109C>A	p.Arg37Arg	synonymous	Exon 6 of 10	ENSP00000479254.1	Q8IVZ9

Frequencies

GnomAD3 genomes Cov.: 33

GnomAD2 exomes AF: 0.00000638 AC: 1 AN: 156836 AF XY: 0.0000120

Gnomad AFR exome AF: 0.00

Gnomad AMR exome AF: 0.00

Gnomad ASJ exome AF: 0.00

Gnomad EAS exome AF: 0.00

Gnomad FIN exome AF: 0.00

Gnomad NFE exome AF: 0.0000162

Gnomad OTH exome AF: 0.00

GnomAD4 exome AF: 0.00000928 AC: 13 AN: 1400240 Hom.: 0 Cov.: 33 AF XY: 0.0000116 AC XY: 8 AN XY: 690830

African (AFR) AF: 0.00 AC: 0 AN: 31646

American (AMR) AF: 0.00 AC: 0 AN: 35882

Ashkenazi Jewish (ASJ) AF: 0.00 AC: 0 AN: 25194

East Asian (EAS) AF: 0.00 AC: 0 AN: 35780

South Asian (SAS) AF: 0.00 AC: 0 AN: 79272

European-Finnish (FIN) AF: 0.00 AC: 0 AN: 48646

Middle Eastern (MID) AF: 0.00 AC: 0 AN: 5694

European-Non Finnish (NFE) AF: 0.0000120 AC: 13 AN: 1080010

Other (OTH) AF: 0.00 AC: 0 AN: 58116

GnomAD4 genome Cov.: 33

ClinVar

ClinVar submissions

Significance: Likely benign

Revision: criteria provided, multiple submitters, no conflicts

Pathogenic	VUS	Benign	Condition
-	-	1	not provided (1)
-	-	1	not specified (1)

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.43
CADD	Benign	8.4
DANN	Benign	0.43
PhyloP100		2.6

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: rs786205493; hg19: chr15-72104318;