NM_014249.4:c.119-28T>C

Variant names:

• chr15-71811455-T-C
• rs2742318
• NM_014249.4:c.119-28T>C

Variant summary

Our verdict is Benign. The variant received -20 ACMG points: 0P and 20B. BP4_Strong BP6_Very_Strong BA1

The NM_014249.4(NR2E3):​c.119-28T>C variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0488 in 1,502,626 control chromosomes in the GnomAD database, including 4,405 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Likely benign (★★).

• Frequency:
  • Genomes: 𝑓 0.10 (1303 hom., cov: 32)
  • Exomes 𝑓: 0.043 (3102 hom.)
• Consequence: NR2E3 NM_014249.4 intron
• Clinical Significance: Benign/Likely benign criteria provided, multiple submitters, no conflicts B:3
• Conservation: PhyloP100: 0.0690
• Publications: 2 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 -20 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.88).
• BP6: Variant 15-71811455-T-C is Benign according to our data. Variant chr15-71811455-T-C is described in ClinVar as Benign/Likely_benign. ClinVar VariationId is 260366.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars.
• BA1: GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.25 is higher than 0.05.

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.119-28T>C		intron	N/A	NP_055064.1	Q9Y5X4-1
	NR2E3	NM_016346.4		c.119-28T>C		intron	N/A	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.119-28T>C		intron	N/A	ENSP00000482504.1	Q9Y5X4-1
	NR2E3	ENST00000621098.1	TSL:1	c.119-28T>C		intron	N/A	ENSP00000479962.1	Q9Y5X4-2
	NR2E3	ENST00000621736.4	TSL:2	c.-146-28T>C		intron	N/A	ENSP00000479254.1	Q8IVZ9

Frequencies

GnomAD3 genomes AF: 0.104 AC: 14838 AN: 143252 Hom.: 1297 Cov.: 32

Gnomad AFR AF: 0.254

Gnomad AMI AF: 0.0443

Gnomad AMR AF: 0.109

Gnomad ASJ AF: 0.0184

Gnomad EAS AF: 0.205

Gnomad SAS AF: 0.0692

Gnomad FIN AF: 0.0449

Gnomad MID AF: 0.0513

Gnomad NFE AF: 0.0317

Gnomad OTH AF: 0.0927

GnomAD2 exomes AF: 0.0722 AC: 11125 AN: 154168 AF XY: 0.0671

Gnomad AFR exome AF: 0.217

Gnomad AMR exome AF: 0.130

Gnomad ASJ exome AF: 0.0198

Gnomad EAS exome AF: 0.199

Gnomad FIN exome AF: 0.0377

Gnomad NFE exome AF: 0.0288

Gnomad OTH exome AF: 0.0594

GnomAD4 exome AF: 0.0430 AC: 58487 AN: 1359280 Hom.: 3102 Cov.: 32 AF XY: 0.0430 AC XY: 28870 AN XY: 670768

African (AFR) AF: 0.260 AC: 6776 AN: 26026

American (AMR) AF: 0.132 AC: 4589 AN: 34662

Ashkenazi Jewish (ASJ) AF: 0.0198 AC: 489 AN: 24732

East Asian (EAS) AF: 0.242 AC: 8550 AN: 35392

South Asian (SAS) AF: 0.0579 AC: 4551 AN: 78576

European-Finnish (FIN) AF: 0.0398 AC: 1817 AN: 45616

Middle Eastern (MID) AF: 0.0584 AC: 248 AN: 4250

European-Non Finnish (NFE) AF: 0.0267 AC: 28194 AN: 1054280

Other (OTH) AF: 0.0587 AC: 3273 AN: 55746

GnomAD4 genome AF: 0.104 AC: 14890 AN: 143346 Hom.: 1303 Cov.: 32 AF XY: 0.104 AC XY: 7256 AN XY: 69942

African (AFR) AF: 0.254 AC: 9043 AN: 35540

American (AMR) AF: 0.109 AC: 1601 AN: 14650

Ashkenazi Jewish (ASJ) AF: 0.0184 AC: 63 AN: 3430

East Asian (EAS) AF: 0.205 AC: 1049 AN: 5126

South Asian (SAS) AF: 0.0691 AC: 332 AN: 4808

European-Finnish (FIN) AF: 0.0449 AC: 441 AN: 9824

Middle Eastern (MID) AF: 0.0552 AC: 16 AN: 290

European-Non Finnish (NFE) AF: 0.0317 AC: 2114 AN: 66790

Other (OTH) AF: 0.0962 AC: 191 AN: 1986

Alfa AF: 0.0195 Hom.: 22

ClinVar

ClinVar submissions

Significance: Benign/Likely benign

Revision: criteria provided, multiple submitters, no conflicts

Pathogenic	VUS	Benign	Condition
-	-	2	not provided (2)
-	-	1	not specified (1)

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.88
CADD	Benign	1.1
DANN	Benign	0.58
PhyloP100		0.069

Splicing

Name	Calibrated prediction	Score	Prediction
SpliceAI score (max)		0.070		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: rs2742318; hg19: chr15-72103795; COSMIC: COSV58909428;