14-24081063-T-A
Position:
Variant summary
Our verdict is Benign. Variant got -14 ACMG points: 0P and 14B. BP4_StrongBP6_ModerateBS1BS2
The NM_001354768.3(NRL):c.*173A>T variant causes a 3 prime UTR change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00117 in 426,294 control chromosomes in the GnomAD database, including 10 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★).
Frequency
Genomes: 𝑓 0.0015 ( 5 hom., cov: 33)
Exomes 𝑓: 0.00097 ( 5 hom. )
Consequence
NRL
NM_001354768.3 3_prime_UTR
NM_001354768.3 3_prime_UTR
Scores
2
Clinical Significance
Conservation
PhyloP100: 0.0950
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]
Genome browser will be placed here
ACMG classification
Classification made for transcript
Verdict is Benign. Variant got -14 ACMG points.
BP4
Computational evidence support a benign effect (BayesDel_noAF=-0.58).
BP6
Variant 14-24081063-T-A is Benign according to our data. Variant chr14-24081063-T-A is described in ClinVar as [Benign]. Clinvar id is 312937.Status of the report is criteria_provided_single_submitter, 1 stars.
BS1
Variant frequency is greater than expected in population sas. gnomad4 allele frequency = 0.00151 (230/152306) while in subpopulation SAS AF= 0.0443 (214/4828). AF 95% confidence interval is 0.0395. There are 5 homozygotes in gnomad4. There are 163 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/exons | MANE | Protein | UniProt |
---|---|---|---|---|---|---|---|---|
NRL | NM_001354768.3 | c.*173A>T | 3_prime_UTR_variant | 3/3 | ENST00000561028.6 | NP_001341697.1 |
Ensembl
Gene | Transcript | HGVSc | HGVSp | Effect | #exon/exons | TSL | MANE | Protein | Appris | UniProt |
---|---|---|---|---|---|---|---|---|---|---|
NRL | ENST00000561028.6 | c.*173A>T | 3_prime_UTR_variant | 3/3 | 2 | NM_001354768.3 | ENSP00000454062 | P1 |
Frequencies
GnomAD3 genomes AF: 0.00152 AC: 232AN: 152188Hom.: 5 Cov.: 33
GnomAD3 genomes
AF:
AC:
232
AN:
152188
Hom.:
Cov.:
33
Gnomad AFR
AF:
Gnomad AMI
AF:
Gnomad AMR
AF:
Gnomad ASJ
AF:
Gnomad EAS
AF:
Gnomad SAS
AF:
Gnomad FIN
AF:
Gnomad MID
AF:
Gnomad NFE
AF:
Gnomad OTH
AF:
GnomAD4 exome AF: 0.000974 AC: 267AN: 273988Hom.: 5 Cov.: 4 AF XY: 0.00125 AC XY: 174AN XY: 138932
GnomAD4 exome
AF:
AC:
267
AN:
273988
Hom.:
Cov.:
4
AF XY:
AC XY:
174
AN XY:
138932
Gnomad4 AFR exome
AF:
Gnomad4 AMR exome
AF:
Gnomad4 ASJ exome
AF:
Gnomad4 EAS exome
AF:
Gnomad4 SAS exome
AF:
Gnomad4 FIN exome
AF:
Gnomad4 NFE exome
AF:
Gnomad4 OTH exome
AF:
GnomAD4 genome AF: 0.00151 AC: 230AN: 152306Hom.: 5 Cov.: 33 AF XY: 0.00219 AC XY: 163AN XY: 74480
GnomAD4 genome
AF:
AC:
230
AN:
152306
Hom.:
Cov.:
33
AF XY:
AC XY:
163
AN XY:
74480
Gnomad4 AFR
AF:
Gnomad4 AMR
AF:
Gnomad4 ASJ
AF:
Gnomad4 EAS
AF:
Gnomad4 SAS
AF:
Gnomad4 FIN
AF:
Gnomad4 NFE
AF:
Gnomad4 OTH
AF:
Alfa
AF:
Hom.:
Bravo
AF:
Asia WGS
AF:
AC:
69
AN:
3478
ClinVar
Significance: Benign
Submissions summary: Benign:1
Revision: criteria provided, single submitter
LINK: link
Submissions by phenotype
Retinitis pigmentosa Benign:1
Benign, criteria provided, single submitter | clinical testing | Illumina Laboratory Services, Illumina | Jan 12, 2018 | 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:
Name
Calibrated prediction
Score
Prediction
BayesDel_noAF
Benign
CADD
Benign
DANN
Benign
Splicing
Name
Calibrated prediction
Score
Prediction
SpliceAI score (max)
Details are displayed if max score is > 0.2
Find out detailed SpliceAI scores and Pangolin per-transcript scores at