chr15-71810534-C-T

Variant summary

Our verdict is Benign. Variant got -20 ACMG points: 0P and 20B. BP4_StrongBP6_Very_StrongBS1BS2

The ENST00000621736.4(NR2E3):​c.-146-949C>T variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.000862 in 584,906 control chromosomes in the GnomAD database, including 3 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Likely benign (★★).

Frequency

Genomes: 𝑓 0.00072 ( 0 hom., cov: 32)
Exomes 𝑓: 0.00091 ( 3 hom. )

Consequence

NR2E3
ENST00000621736.4 intron

Scores

2

Clinical Significance

Likely benign criteria provided, multiple submitters, no conflicts B:3

Conservation

PhyloP100: -0.0320
Variant links:
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]

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ACMG classification

Classification made for transcript

Verdict is Benign. Variant got -20 ACMG points.

BP4
Computational evidence support a benign effect (BayesDel_noAF=-0.83).
BP6
Variant 15-71810534-C-T is Benign according to our data. Variant chr15-71810534-C-T is described in ClinVar as [Likely_benign]. Clinvar id is 888357.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars.
BS1
Variant frequency is greater than expected in population sas. gnomad4 allele frequency = 0.000723 (110/152244) while in subpopulation SAS AF= 0.00747 (36/4820). AF 95% confidence interval is 0.00555. There are 0 homozygotes in gnomad4. There are 61 alleles in male gnomad4 subpopulation. Median coverage is 32. This position pass quality control queck.
BS2
High Homozygotes in GnomAdExome4 at 3 AD,AR gene

Transcripts

RefSeq

Gene Transcript HGVSc HGVSp Effect #exon/exons MANE UniProt
NR2E3NM_014249.4 linkuse as main transcript upstream_gene_variant ENST00000617575.5
NR2E3NM_016346.4 linkuse as main transcript upstream_gene_variant

Ensembl

Gene Transcript HGVSc HGVSp Effect #exon/exons TSL MANE Appris UniProt
NR2E3ENST00000621736.4 linkuse as main transcriptc.-146-949C>T intron_variant 2
NR2E3ENST00000617575.5 linkuse as main transcript upstream_gene_variant 1 NM_014249.4 P1Q9Y5X4-1

Frequencies

GnomAD3 genomes
AF:
0.000723
AC:
110
AN:
152126
Hom.:
0
Cov.:
32
show subpopulations
Gnomad AFR
AF:
0.0000966
Gnomad AMI
AF:
0.00
Gnomad AMR
AF:
0.00151
Gnomad ASJ
AF:
0.000577
Gnomad EAS
AF:
0.00
Gnomad SAS
AF:
0.00746
Gnomad FIN
AF:
0.00
Gnomad MID
AF:
0.00
Gnomad NFE
AF:
0.000588
Gnomad OTH
AF:
0.00239
GnomAD4 exome
AF:
0.000911
AC:
394
AN:
432662
Hom.:
3
Cov.:
6
AF XY:
0.00114
AC XY:
255
AN XY:
224548
show subpopulations
Gnomad4 AFR exome
AF:
0.000253
Gnomad4 AMR exome
AF:
0.000856
Gnomad4 ASJ exome
AF:
0.000339
Gnomad4 EAS exome
AF:
0.0000386
Gnomad4 SAS exome
AF:
0.00490
Gnomad4 FIN exome
AF:
0.0000382
Gnomad4 NFE exome
AF:
0.000515
Gnomad4 OTH exome
AF:
0.000978
GnomAD4 genome
AF:
0.000723
AC:
110
AN:
152244
Hom.:
0
Cov.:
32
AF XY:
0.000820
AC XY:
61
AN XY:
74420
show subpopulations
Gnomad4 AFR
AF:
0.0000963
Gnomad4 AMR
AF:
0.00150
Gnomad4 ASJ
AF:
0.000577
Gnomad4 EAS
AF:
0.00
Gnomad4 SAS
AF:
0.00747
Gnomad4 FIN
AF:
0.00
Gnomad4 NFE
AF:
0.000588
Gnomad4 OTH
AF:
0.00237
Alfa
AF:
0.000741
Hom.:
0
Bravo
AF:
0.000650
Asia WGS
AF:
0.00231
AC:
8
AN:
3478

ClinVar

Significance: Likely benign
Submissions summary: Benign:3
Revision: criteria provided, multiple submitters, no conflicts
LINK: link

Submissions by phenotype

Enhanced S-cone syndrome Benign:1
Likely benign, criteria provided, single submitterclinical testingIllumina Laboratory Services, IlluminaJan 13, 2018This variant was observed in the ICSL laboratory as part of a predisposition screen in an ostensibly healthy population. It had not been previously curated by ICSL or reported in the Human Gene Mutation Database (HGMD: prior to June 1st, 2018), and was therefore a candidate for classification through an automated scoring system. Utilizing variant allele frequency, disease prevalence and penetrance estimates, and inheritance mode, an automated score was calculated to assess if this variant is too frequent to cause the disease. Based on the score and internal cut-off values, a variant classified as likely benign is not then subjected to further curation. The score for this variant resulted in a classification of likely benign for this disease. -
not provided Benign:1
Likely benign, criteria provided, single submitternot providedBreakthrough Genomics, Breakthrough Genomics-- -
Retinitis pigmentosa Benign:1
Likely benign, criteria provided, single submitterclinical testingIllumina Laboratory Services, IlluminaJan 13, 2018This variant was observed in the ICSL laboratory as part of a predisposition screen in an ostensibly healthy population. It had not been previously curated by ICSL or reported in the Human Gene Mutation Database (HGMD: prior to June 1st, 2018), and was therefore a candidate for classification through an automated scoring system. Utilizing variant allele frequency, disease prevalence and penetrance estimates, and inheritance mode, an automated score was calculated to assess if this variant is too frequent to cause the disease. Based on the score and internal cut-off values, a variant classified as likely benign is not then subjected to further curation. The score for this variant resulted in a classification of likely benign for this disease. -

Computational scores

Source: dbNSFP v4.3

Name
Calibrated prediction
Score
Prediction
BayesDel_noAF
Benign
-0.83
CADD
Benign
5.3
DANN
Benign
0.64

Splicing

Find out detailed SpliceAI scores and Pangolin per-transcript scores at spliceailookup.broadinstitute.org

Publications

LitVar

Below is the list of publications found by LitVar. It may be empty.

Other links and lift over

dbSNP: rs528679282; hg19: chr15-72102874; API