chr15-71810752-C-T

Variant names:

• chr15-71810752-C-T
• rs570230953
• NM_014249.4:c.9C>T

Variant summary

Our verdict is Benign. The variant received -7 ACMG points: 0P and 7B. BP4_Strong BP6_Moderate BP7

The NM_014249.4(NR2E3):​c.9C>T​(p.Thr3Thr) variant causes a synonymous change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00000637 in 1,569,698 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: 𝑓 0.0000066 (0 hom., cov: 32)
  • Exomes 𝑓: 0.0000063 (0 hom.)
• Consequence: NR2E3 NM_014249.4 synonymous
• Clinical Significance: Likely benign criteria provided, single submitter B:1
• Conservation: PhyloP100: -1.76
• 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: Benign. The variant received -7 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.83).
• BP6: Variant 15-71810752-C-T is Benign according to our data. Variant chr15-71810752-C-T is described in ClinVar as Likely_benign. ClinVar VariationId is 2421715.Status of the report is criteria_provided_single_submitter, 1 stars.
• BP7: Synonymous conserved (PhyloP=-1.76 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.9C>T	p.Thr3Thr	synonymous	Exon 1 of 8	NP_055064.1	Q9Y5X4-1
	NR2E3	NM_016346.4		c.9C>T	p.Thr3Thr	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.9C>T	p.Thr3Thr	synonymous	Exon 1 of 8	ENSP00000482504.1	Q9Y5X4-1
	NR2E3	ENST00000621098.1	TSL:1	c.9C>T	p.Thr3Thr	synonymous	Exon 1 of 7	ENSP00000479962.1	Q9Y5X4-2
	NR2E3	ENST00000621736.4	TSL:2	c.-146-731C>T		intron	N/A	ENSP00000479254.1	Q8IVZ9

Frequencies

GnomAD3 genomes AF: 0.00000657 AC: 1 AN: 152176 Hom.: 0 Cov.: 32

Gnomad AFR AF: 0.00

Gnomad AMI AF: 0.00

Gnomad AMR AF: 0.00

Gnomad ASJ AF: 0.00

Gnomad EAS AF: 0.00

Gnomad SAS AF: 0.000207

Gnomad FIN AF: 0.00

Gnomad MID AF: 0.00

Gnomad NFE AF: 0.00

Gnomad OTH AF: 0.00

GnomAD2 exomes AF: 0.0000168 AC: 3 AN: 179090 AF XY: 0.0000208

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: 0.0000133

Gnomad OTH exome AF: 0.00

GnomAD4 exome AF: 0.00000635 AC: 9 AN: 1417404 Hom.: 0 Cov.: 31 AF XY: 0.00000856 AC XY: 6 AN XY: 700898

African (AFR) AF: 0.00 AC: 0 AN: 32228

American (AMR) AF: 0.00 AC: 0 AN: 38138

Ashkenazi Jewish (ASJ) AF: 0.00 AC: 0 AN: 25400

East Asian (EAS) AF: 0.00 AC: 0 AN: 36810

South Asian (SAS) AF: 0.0000872 AC: 7 AN: 80270

European-Finnish (FIN) AF: 0.00 AC: 0 AN: 50036

Middle Eastern (MID) AF: 0.00 AC: 0 AN: 5684

European-Non Finnish (NFE) AF: 0.00000183 AC: 2 AN: 1090046

Other (OTH) AF: 0.00 AC: 0 AN: 58792

GnomAD4 genome AF: 0.00000657 AC: 1 AN: 152294 Hom.: 0 Cov.: 32 AF XY: 0.0000134 AC XY: 1 AN XY: 74464

African (AFR) AF: 0.00 AC: 0 AN: 41558

American (AMR) AF: 0.00 AC: 0 AN: 15302

Ashkenazi Jewish (ASJ) AF: 0.00 AC: 0 AN: 3472

East Asian (EAS) AF: 0.00 AC: 0 AN: 5172

South Asian (SAS) AF: 0.000207 AC: 1 AN: 4822

European-Finnish (FIN) AF: 0.00 AC: 0 AN: 10628

Middle Eastern (MID) AF: 0.00 AC: 0 AN: 294

European-Non Finnish (NFE) AF: 0.00 AC: 0 AN: 68018

Other (OTH) AF: 0.00 AC: 0 AN: 2116

Alfa AF: 0.00 Hom.: 0

Bravo AF: 0.00000378

ClinVar

ClinVar submissions

Significance: Likely benign

Revision: criteria provided, single submitter

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

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.83
CADD	Benign	0.81
DANN	Benign	0.69
PhyloP100		-1.8
PromoterAI		0.0063	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: rs570230953; hg19: chr15-72103092;