14-24081239-G-C

Variant summary

Our verdict is Benign. Variant got -21 ACMG points: 0P and 21B. BP4_StrongBP6_Very_StrongBP7BS1BS2

The NM_001354768.3(NRL):ā€‹c.711C>Gā€‹(p.Leu237Leu) variant causes a synonymous change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.000779 in 1,492,974 control chromosomes in the GnomAD database, including 9 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (ā˜…ā˜…).

Frequency

Genomes: š‘“ 0.0042 ( 5 hom., cov: 33)
Exomes š‘“: 0.00040 ( 4 hom. )

Consequence

NRL
NM_001354768.3 synonymous

Scores

2

Clinical Significance

Benign criteria provided, multiple submitters, no conflicts B:7

Conservation

PhyloP100: 0.980
Variant links:
Genes affected
NRL (HGNC:8002): (neural retina leucine zipper) This gene encodes a basic motif-leucine zipper transcription factor of the Maf subfamily. The encoded protein is conserved among vertebrates and is a critical intrinsic regulator of photoceptor development and function. Mutations in this gene have been associated with retinitis pigmentosa and retinal degenerative diseases. [provided by RefSeq, Jul 2008]

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ACMG classification

Classification made for transcript

Verdict is Benign. Variant got -21 ACMG points.

BP4
Computational evidence support a benign effect (BayesDel_noAF=-0.55).
BP6
Variant 14-24081239-G-C is Benign according to our data. Variant chr14-24081239-G-C is described in ClinVar as [Benign]. Clinvar id is 167386.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars. Variant chr14-24081239-G-C is described in Lovd as [Benign].
BP7
Synonymous conserved (PhyloP=0.98 with no splicing effect.
BS1
Variant frequency is greater than expected in population afr. gnomad4 allele frequency = 0.00416 (633/152294) while in subpopulation AFR AF= 0.0145 (602/41558). AF 95% confidence interval is 0.0135. There are 5 homozygotes in gnomad4. There are 295 alleles in male gnomad4 subpopulation. Median coverage is 33. This position pass quality control queck.
BS2
High Homozygotes in GnomAd4 at 5 AD,AR gene

Transcripts

RefSeq

Gene Transcript HGVSc HGVSp Effect Exon rank MANE Protein UniProt
NRLNM_001354768.3 linkc.711C>G p.Leu237Leu synonymous_variant Exon 3 of 3 ENST00000561028.6 NP_001341697.1

Ensembl

Gene Transcript HGVSc HGVSp Effect Exon rank TSL MANE Protein Appris UniProt
NRLENST00000561028.6 linkc.711C>G p.Leu237Leu synonymous_variant Exon 3 of 3 2 NM_001354768.3 ENSP00000454062.2 P54845-1

Frequencies

GnomAD3 genomes
AF:
0.00411
AC:
625
AN:
152176
Hom.:
5
Cov.:
33
show subpopulations
Gnomad AFR
AF:
0.0144
Gnomad AMI
AF:
0.00
Gnomad AMR
AF:
0.00131
Gnomad ASJ
AF:
0.00
Gnomad EAS
AF:
0.00
Gnomad SAS
AF:
0.00
Gnomad FIN
AF:
0.00
Gnomad MID
AF:
0.00
Gnomad NFE
AF:
0.0000588
Gnomad OTH
AF:
0.00287
GnomAD3 exomes
AF:
0.000445
AC:
52
AN:
116982
Hom.:
0
AF XY:
0.000309
AC XY:
20
AN XY:
64730
show subpopulations
Gnomad AFR exome
AF:
0.0113
Gnomad AMR exome
AF:
0.000699
Gnomad ASJ exome
AF:
0.00
Gnomad EAS exome
AF:
0.00
Gnomad SAS exome
AF:
0.00
Gnomad FIN exome
AF:
0.00
Gnomad NFE exome
AF:
0.0000218
Gnomad OTH exome
AF:
0.000332
GnomAD4 exome
AF:
0.000395
AC:
530
AN:
1340680
Hom.:
4
Cov.:
30
AF XY:
0.000311
AC XY:
206
AN XY:
661578
show subpopulations
Gnomad4 AFR exome
AF:
0.0157
Gnomad4 AMR exome
AF:
0.000865
Gnomad4 ASJ exome
AF:
0.00
Gnomad4 EAS exome
AF:
0.00
Gnomad4 SAS exome
AF:
0.0000280
Gnomad4 FIN exome
AF:
0.00
Gnomad4 NFE exome
AF:
0.00000666
Gnomad4 OTH exome
AF:
0.000940
GnomAD4 genome
AF:
0.00416
AC:
633
AN:
152294
Hom.:
5
Cov.:
33
AF XY:
0.00396
AC XY:
295
AN XY:
74474
show subpopulations
Gnomad4 AFR
AF:
0.0145
Gnomad4 AMR
AF:
0.00131
Gnomad4 ASJ
AF:
0.00
Gnomad4 EAS
AF:
0.00
Gnomad4 SAS
AF:
0.000207
Gnomad4 FIN
AF:
0.00
Gnomad4 NFE
AF:
0.0000588
Gnomad4 OTH
AF:
0.00284
Alfa
AF:
0.000337
Hom.:
0
Bravo
AF:
0.00481
Asia WGS
AF:
0.00173
AC:
6
AN:
3478

ClinVar

Significance: Benign
Submissions summary: Benign:7
Revision: criteria provided, multiple submitters, no conflicts
LINK: link

Submissions by phenotype

not specified Benign:3
Dec 17, 2013
Eurofins Ntd Llc (ga)
Significance: Benign
Review Status: criteria provided, single submitter
Collection Method: clinical testing

- -

-
Clinical Genetics, Academic Medical Center
Significance: Benign
Review Status: no assertion criteria provided
Collection Method: clinical testing

- -

-
Clinical Genetics DNA and cytogenetics Diagnostics Lab, Erasmus MC, Erasmus Medical Center
Significance: Benign
Review Status: no assertion criteria provided
Collection Method: clinical testing

- -

not provided Benign:3
Nov 22, 2023
ARUP Laboratories, Molecular Genetics and Genomics, ARUP Laboratories
Significance: Benign
Review Status: criteria provided, single submitter
Collection Method: clinical testing

- -

Jan 29, 2025
Labcorp Genetics (formerly Invitae), Labcorp
Significance: Benign
Review Status: criteria provided, single submitter
Collection Method: clinical testing

- -

-
Breakthrough Genomics, Breakthrough Genomics
Significance: Benign
Review Status: criteria provided, single submitter
Collection Method: not provided

- -

Retinitis pigmentosa Benign:1
Jan 13, 2018
Illumina Laboratory Services, Illumina
Significance: Benign
Review Status: criteria provided, single submitter
Collection Method: clinical testing

This 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 benign is not then subjected to further curation. The score for this variant resulted in a classification of benign for this disease. -

Computational scores

Source: dbNSFP v4.3

Name
Calibrated prediction
Score
Prediction
BayesDel_noAF
Benign
-0.55
CADD
Benign
6.3
DANN
Benign
0.55

Splicing

Name
Calibrated prediction
Score
Prediction
SpliceAI score (max)
0.020
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

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

Other links and lift over

dbSNP: rs8009051; hg19: chr14-24550448; API