Variant 14-24080952-AC-A details in Genebe, Genetics Data Aggregator

Variant summary

Our verdict is Likely benign. Variant got -5 ACMG points: 0P and 5B. BS1_SupportingBS2

The NM_001354768.3(NRL):c.*283del variant causes a 3 prime UTR change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.000799 in 333,056 control chromosomes in the GnomAD database, including 3 homozygotes. Variant has been reported in ClinVar as Uncertain significance (★).

Frequency

Genomes: 𝑓 0.00042 ( 1 hom., cov: 32)

Exomes 𝑓: 0.0011 ( 2 hom. )

Consequence

NRL
NM_001354768.3 3_prime_UTR

Scores

Not classified

Clinical Significance

Uncertain significance criteria provided, single submitter U:1

Conservation

PhyloP100: -0.394

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:

Genome browser will be placed here

ACMG classification

Classification made for transcript

Verdict is Likely_benign. Variant got -5 ACMG points.

BS1

Variant frequency is greater than expected in population eas. gnomad4 allele frequency = 0.000423 (64/151122) while in subpopulation EAS AF= 0.0109 (56/5116). AF 95% confidence interval is 0.00866. There are 1 homozygotes in gnomad4. There are 37 alleles in male gnomad4 subpopulation. Median coverage is 32. This position pass quality control queck. Existence of Clinvar submissions makes me limit the strength of this signal to Supporting

BS2

High Homozygotes in GnomAdExome4 at 2 AD,AR gene

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
NRL	NM_001354768.3 linkuse as main transcript	c.*283del		3_prime_UTR_variant	3/3	ENST00000561028.6	NP_001341697.1

Ensembl

Gene	Transcript	HGVSc	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
NRL	ENST00000561028.6 linkuse as main transcript	c.*283del	3_prime_UTR_variant	3/3	2	NM_001354768.3	ENSP00000454062	P1	P54845-1
NRL	ENST00000396997.1 linkuse as main transcript	c.*283del	3_prime_UTR_variant	4/4	1		ENSP00000380193	P1	P54845-1
NRL	ENST00000397002.6 linkuse as main transcript	c.*283del	3_prime_UTR_variant	3/3	1		ENSP00000380197	P1	P54845-1
NRL	ENST00000560550.1 linkuse as main transcript		downstream_gene_variant		1		ENSP00000452966		P54845-2

Frequencies

GnomAD3 genomes

AF:

0.000424

AC:

AN:

151004

Hom.:

Cov.:

show subpopulations

Gnomad AFR

AF:

0.00

Gnomad AMI

AF:

0.00

Gnomad AMR

AF:

0.00

Gnomad ASJ

AF:

0.00

Gnomad EAS

AF:

0.0109

Gnomad SAS

AF:

0.00169

Gnomad FIN

AF:

0.00

Gnomad MID

AF:

0.00

Gnomad NFE

AF:

0.00

Gnomad OTH

AF:

0.00

GnomAD4 exome

AF:

0.00111

AC:

202

AN:

181934

Hom.:

Cov.:

AF XY:

0.00101

AC XY:

AN XY:

91856

show subpopulations

Gnomad4 AFR exome

AF:

0.00

Gnomad4 AMR exome

AF:

0.00

Gnomad4 ASJ exome

AF:

0.00

Gnomad4 EAS exome

AF:

0.0116

Gnomad4 SAS exome

AF:

0.000576

Gnomad4 FIN exome

AF:

0.0000633

Gnomad4 NFE exome

AF:

0.0000427

Gnomad4 OTH exome

AF:

0.000245

GnomAD4 genome

AF:

0.000423

AC:

AN:

151122

Hom.:

Cov.:

AF XY:

0.000502

AC XY:

AN XY:

73778

show subpopulations

Gnomad4 AFR

AF:

0.00

Gnomad4 AMR

AF:

0.00

Gnomad4 ASJ

AF:

0.00

Gnomad4 EAS

AF:

0.0109

Gnomad4 SAS

AF:

0.00169

Gnomad4 FIN

AF:

0.00

Gnomad4 NFE

AF:

0.00

Gnomad4 OTH

AF:

0.00

Bravo

AF:

0.000465

Asia WGS

AF:

0.00173

AC:

AN:

3478

ClinVar

Significance: Uncertain significance

Submissions summary: Uncertain:1

Revision: criteria provided, single submitter

LINK: link

Submissions by phenotype

Retinitis Pigmentosa, Dominant

Uncertain:1

Uncertain significance, criteria provided, single submitter

clinical testing

Illumina Laboratory Services, Illumina

Jun 14, 2016

- -

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

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