Variant 14-24081237-C-A details in Genebe, Genetics Data Aggregator

Variant summary

Our verdict is Likely benign. Variant got -2 ACMG points: 0P and 2B. BP4_Moderate

The NM_001354768.3(NRL):c.713G>T(p.Ter238LeuextTer58) variant causes a stop lost change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00000598 in 1,337,952 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 Uncertain significance (★).

Frequency

Genomes: not found (cov: 33)

Exomes 𝑓: 0.0000060 ( 0 hom. )

Consequence

NRL
NM_001354768.3 stop_lost

Scores

Clinical Significance

Uncertain significance criteria provided, single submitter P:1U:1

Conservation

PhyloP100: 1.71

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]

NRL links:

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ACMG classification

Classification made for transcript

Verdict is Likely_benign. Variant got -2 ACMG points.

BP4

Computational evidence support a benign effect (BayesDel_addAF=-0.166867).

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
NRL	NM_001354768.3 linkuse as main transcript	c.713G>T	p.Ter238LeuextTer58	stop_lost	3/3	ENST00000561028.6

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
NRL	ENST00000561028.6 linkuse as main transcript	c.713G>T	p.Ter238LeuextTer58	stop_lost	3/3	2	NM_001354768.3	P1	P54845-1

Frequencies

GnomAD3 genomes

Cov.:

GnomAD3 exomes

AF:

0.00000866

AC:

AN:

115494

Hom.:

AF XY:

0.00

AC XY:

AN XY:

63964

show subpopulations

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 SAS exome

AF:

0.0000538

Gnomad FIN exome

AF:

0.00

Gnomad NFE exome

AF:

0.00

Gnomad OTH exome

AF:

0.00

GnomAD4 exome

AF:

0.00000598

AC:

AN:

1337952

Hom.:

Cov.:

AF XY:

0.00000757

AC XY:

AN XY:

660188

show subpopulations

Gnomad4 AFR exome

AF:

0.00

Gnomad4 AMR exome

AF:

0.00

Gnomad4 ASJ exome

AF:

0.00

Gnomad4 EAS exome

AF:

0.00

Gnomad4 SAS exome

AF:

0.0000985

Gnomad4 FIN exome

AF:

0.00

Gnomad4 NFE exome

AF:

9.53e-7

Gnomad4 OTH exome

AF:

0.00

GnomAD4 genome

Cov.:

ExAC

AF:

0.00000920

AC:

ClinVar

Significance: Uncertain significance

Submissions summary: Pathogenic:1Uncertain:1

Revision: criteria provided, single submitter

LINK: link

Submissions by phenotype

Retinitis pigmentosa

Pathogenic:1Uncertain:1

Uncertain significance, criteria provided, single submitter	curation	Broad Center for Mendelian Genomics, Broad Institute of MIT and Harvard	Apr 01, 2021	The p.Ter238LeuextTer58 variant in NRL was identified in an individual with Retinitis pigmentosa, via a collaborative study between the Broad Institute's Center for Mendelian Genomics and the Pierce lab (https://oculargenomics.meei.harvard.edu/labs/pierce-lab/lab-members/). Through a review of available evidence we were able to apply the following criteria: PM2, PM4. Based on this evidence we have classified this variant as a Variant of Uncertain Significance. If you have any questions about the classification please reach out to the Pierce Lab. -
Pathogenic, no assertion criteria provided	research	Leeds Institute of Medical Research, University of Leeds	Jan 15, 2021	- -

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

BayesDel_addAF

Benign

-0.17

BayesDel_noAF

Benign

-0.48

Cadd

Benign

Dann

Benign

0.79

Eigen

Uncertain

0.67

Eigen_PC

Uncertain

0.44

FATHMM_MKL

Uncertain

0.92

MutationTaster

Benign

1.0

N;N;N;N;N

Vest4

0.33

GERP RS

4.1

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

Publications

LitVar

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

Variant summary

Frequency

Consequence

Scores

Clinical Significance

Conservation

ACMG classification

Transcripts

RefSeq

Ensembl

Frequencies

ClinVar

Submissions by phenotype

Computational scores

Splicing

Publications

LitVar

Other links and lift over