rs786205493

Variant names:

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

Your query was ambiguous. Multiple possible variants found:

• chr15-71811978-C-A
• chr15-71811978-C-G
• chr15-71811978-C-T

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

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

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 id 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.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
NR2E3	NM_014249.4	c.373C>A	p.Arg125Arg	synonymous_variant	Exon 4 of 8	ENST00000617575.5	NP_055064.1
NR2E3	NM_016346.4	c.373C>A	p.Arg125Arg	synonymous_variant	Exon 4 of 7		NP_057430.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
NR2E3	ENST00000617575.5	c.373C>A	p.Arg125Arg	synonymous_variant	Exon 4 of 8	1	NM_014249.4	ENSP00000482504.1
NR2E3	ENST00000621098.1	c.373C>A	p.Arg125Arg	synonymous_variant	Exon 4 of 7	1		ENSP00000479962.1
NR2E3	ENST00000621736.4	c.109C>A	p.Arg37Arg	synonymous_variant	Exon 6 of 10	2		ENSP00000479254.1

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

Gnomad4 AFR exome AF: 0.00 AC: 0 AN: 31646

Gnomad4 AMR exome AF: 0.00 AC: 0 AN: 35882

Gnomad4 ASJ exome AF: 0.00 AC: 0 AN: 25194

Gnomad4 EAS exome AF: 0.00 AC: 0 AN: 35780

Gnomad4 SAS exome AF: 0.00 AC: 0 AN: 79272

Gnomad4 FIN exome AF: 0.00 AC: 0 AN: 48646

Gnomad4 NFE exome AF: 0.0000120 AC: 13 AN: 1080010

Gnomad4 Remaining exome AF: 0.00 AC: 0 AN: 58116

GnomAD4 genome Cov.: 33

ClinVar

Significance: Likely benign

Submissions summary: Benign:2

Revision: criteria provided, multiple submitters, no conflicts

Submissions by phenotype

not specified Benign:1

Mar 29, 2024

Women's Health and Genetics/Laboratory Corporation of America, LabCorp

Significance: Likely benign

Review Status: criteria provided, single submitter

Collection Method: clinical testing

Variant summary: NR2E3 c.373C>A alters a conserved nucleotide resulting in a synonymous change. Consensus agreement among computation tools predict no significant impact on normal splicing. However, these predictions have yet to be confirmed by functional studies. The variant allele was found at a frequency of 6.4e-06 in 156836 control chromosomes. The available data on variant occurrences in the general population are insufficient to allow any conclusion about variant significance. To our knowledge, no occurrence of c.373C>A in individuals affected with Retinitis Pigmentosa and no experimental evidence demonstrating its impact on protein function have been reported. ClinVar contains an entry for this variant (Variation ID: 2792014). Based on the evidence outlined above, the variant was classified as likely benign. -

not provided Benign:1

Jun 15, 2023

Labcorp Genetics (formerly Invitae), Labcorp

Significance: Likely benign

Review Status: criteria provided, single submitter

Collection Method: clinical testing

- -

Computational scores

Source: dbNSFP v4.3

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

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

Other links and lift over

dbSNP: rs786205493; hg19: chr15-72104318;