Genetic Variant NM_001354768.3:c.*558C>T (chr14-24080678-G-A) – ACMG Classification: Benign (-14 pts)

Variant summary

Our verdict is Benign. The variant received -14 ACMG points: 0P and 14B. BP4_StrongBP6_ModerateBA1

The NM_001354768.3(NRL):c.*558C>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 0.00701 in 152,698 control chromosomes in the GnomAD database, including 6 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★).

Frequency

Genomes: 𝑓 0.0070 ( 6 hom., cov: 32)

Exomes 𝑓: 0.0021 ( 0 hom. )

Consequence

NRL
NM_001354768.3 3_prime_UTR

Scores

Clinical Significance

Benign criteria provided, single submitter B:1

Conservation

PhyloP100: -1.28

Publications

1 publications found

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 Gene-Disease associations (from GenCC):

retinitis pigmentosa 27
Inheritance: AD, AR Classification: DEFINITIVE, STRONG Submitted by: G2P, Labcorp Genetics (formerly Invitae), ClinGen, Ambry Genetics
enhanced S-cone syndrome
Inheritance: AR Classification: DEFINITIVE Submitted by: Ambry Genetics
retinitis pigmentosa
Inheritance: AD Classification: SUPPORTIVE Submitted by: Orphanet

NRL links:

Genome browser will be placed here

ACMG classification

Classification was made for transcript

Our verdict: Benign. The variant received -14 ACMG points.

BP4

Computational evidence support a benign effect (BayesDel_noAF=-0.75).

BP6

Variant 14-24080678-G-A is Benign according to our data. Variant chr14-24080678-G-A is described in ClinVar as Benign. ClinVar VariationId is 312931.Status of the report is criteria_provided_single_submitter, 1 stars.

BA1

GnomAdExome4 highest subpopulation (AFR) allele frequency = 0.5 is higher than 0.05.

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_001354768.3. You can select a different transcript below to see updated ACMG assignments.

RefSeq Transcripts

Gene	Transcript	Tags	HGVSc	Effect	Exon Rank	Protein	UniProt
NRL	NM_001354768.3	MANE Select	c.*558C>T	3_prime_UTR	Exon 3 of 3	NP_001341697.1	P54845-1
NRL	NM_001354769.1		c.*558C>T	3_prime_UTR	Exon 4 of 4	NP_001341698.1	P54845-1
NRL	NM_006177.5		c.*558C>T	3_prime_UTR	Exon 4 of 4	NP_006168.1	P54845-1

Ensembl Transcripts

Gene	Transcript	Tags	HGVSc	Effect	Exon Rank	Protein	UniProt
NRL	ENST00000561028.6	TSL:2 MANE Select	c.*558C>T	3_prime_UTR	Exon 3 of 3	ENSP00000454062.2	P54845-1
NRL	ENST00000397002.6	TSL:1	c.*558C>T	3_prime_UTR	Exon 3 of 3	ENSP00000380197.2	P54845-1
NRL	ENST00000905081.1		c.*558C>T	3_prime_UTR	Exon 4 of 4	ENSP00000575140.1

Frequencies

GnomAD3 genomes

AF:

0.00702

AC:

1067

AN:

152100

Hom.:

Cov.:

show subpopulations

Gnomad AFR

AF:

0.0189

Gnomad AMI

AF:

0.00

Gnomad AMR

AF:

0.00772

Gnomad ASJ

AF:

0.0153

Gnomad EAS

AF:

0.00

Gnomad SAS

AF:

0.000829

Gnomad FIN

AF:

0.00

Gnomad MID

AF:

0.0158

Gnomad NFE

AF:

0.00121

Gnomad OTH

AF:

0.0115

GnomAD4 exome

AF:

0.00208

AC:

AN:

480

Hom.:

Cov.:

AF XY:

0.00331

AC XY:

AN XY:

302

show subpopulations

African (AFR)

AF:

0.500

AC:

AN:

American (AMR)

AC:

AN:

Ashkenazi Jewish (ASJ)

AF:

0.00

AC:

AN:

East Asian (EAS)

AC:

AN:

South Asian (SAS)

AC:

AN:

European-Finnish (FIN)

AF:

0.00

AC:

AN:

416

Middle Eastern (MID)

AC:

AN:

European-Non Finnish (NFE)

AF:

0.00

AC:

AN:

Other (OTH)

AF:

0.00

AC:

AN:

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.425

Heterozygous variant carriers

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

GnomAD4 genome

AF:

0.00703

AC:

1070

AN:

152218

Hom.:

Cov.:

AF XY:

0.00697

AC XY:

519

AN XY:

74430

show subpopulations

African (AFR)

AF:

0.0189

AC:

784

AN:

41530

American (AMR)

AF:

0.00771

AC:

118

AN:

15296

Ashkenazi Jewish (ASJ)

AF:

0.0153

AC:

AN:

3470

East Asian (EAS)

AF:

0.00

AC:

AN:

5178

South Asian (SAS)

AF:

0.000830

AC:

AN:

4822

European-Finnish (FIN)

AF:

0.00

AC:

AN:

10588

Middle Eastern (MID)

AF:

0.0170

AC:

AN:

294

European-Non Finnish (NFE)

AF:

0.00121

AC:

AN:

68012

Other (OTH)

AF:

0.0113

AC:

AN:

2116

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.501

Heterozygous variant carriers

142

190

237

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Genome Het

Genome Hom

Variant carriers

100

<30

30-35

35-40

40-45

45-50

50-55

55-60

60-65

65-70

70-75

75-80

>80

Age

Alfa

AF:

0.00364

Hom.:

Bravo

AF:

0.00831

Asia WGS

AF:

0.00202

AC:

AN:

3478

ClinVar

ClinVar submissions

Significance:Benign

Revision:criteria provided, single submitter

View on ClinVar

Pathogenic

VUS

Benign

Condition

Retinitis pigmentosa (1)

Computational scores

Source: dbNSFP v4.9

Name

Calibrated prediction

Score

Prediction

BayesDel_noAF

Benign

-0.75

CADD

Benign

0.73

(source)

DANN

Benign

0.75

PhyloP100

-1.3

Mutation Taster

=100/0

polymorphism

(source)

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

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Variant summary

Frequency

Consequence

Scores

Clinical Significance

Conservation

Publications

ACMG classification

Variant Effect in Transcripts

RefSeq Transcripts

Ensembl Transcripts

Frequencies

Age Distribution

ClinVar

Computational scores

Splicing

Publications

Other links and lift over