chr14-24080402-C-G

Variant names:

• chr14-24080402-C-G
• rs1051718
• NM_001354768.3:c.*834G>C

Variant summary

Our verdict is Benign. The variant received -20 ACMG points: 0P and 20B. BP4_Strong BP6_Very_Strong BA1

The NM_001354768.3(NRL):​c.*834G>C variant causes a 3 prime UTR change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0213 in 152,496 control chromosomes in the GnomAD database, including 42 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★★).

• Frequency:
  • Genomes: 𝑓 0.021 (42 hom., cov: 32)
  • Exomes 𝑓: 0.020 (0 hom.)
• Consequence: NRL NM_001354768.3 3_prime_UTR
• Clinical Significance: Benign criteria provided, multiple submitters, no conflicts B:2
• Conservation: PhyloP100: 0.227
• Publications: 2 publications found

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

ACMG classification

Our verdict: Benign. The variant received -20 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.8).
• BP6: Variant 14-24080402-C-G is Benign according to our data. Variant chr14-24080402-C-G is described in ClinVar as Benign. ClinVar VariationId is 312927.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars.
• BA1: GnomAdExome4 highest subpopulation (NFE) allele frequency = 0.0556 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

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	NRL	NM_001354768.3	MANE Select	c.*834G>C		3_prime_UTR	Exon 3 of 3	NP_001341697.1	P54845-1
	NRL	NM_001354769.1		c.*834G>C		3_prime_UTR	Exon 4 of 4	NP_001341698.1	P54845-1
	NRL	NM_006177.5		c.*834G>C		3_prime_UTR	Exon 4 of 4	NP_006168.1	P54845-1

Ensembl Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	NRL	ENST00000561028.6	TSL:2 MANE Select	c.*834G>C		3_prime_UTR	Exon 3 of 3	ENSP00000454062.2	P54845-1
	NRL	ENST00000397002.6	TSL:1	c.*834G>C		3_prime_UTR	Exon 3 of 3	ENSP00000380197.2	P54845-1
	NRL	ENST00000905081.1		c.*834G>C		3_prime_UTR	Exon 4 of 4	ENSP00000575140.1

Frequencies

GnomAD3 genomes AF: 0.0213 AC: 3242 AN: 152180 Hom.: 42 Cov.: 32

Gnomad AFR AF: 0.00504

Gnomad AMI AF: 0.0274

Gnomad AMR AF: 0.0184

Gnomad ASJ AF: 0.0115

Gnomad EAS AF: 0.00

Gnomad SAS AF: 0.00435

Gnomad FIN AF: 0.0287

Gnomad MID AF: 0.00

Gnomad NFE AF: 0.0339

Gnomad OTH AF: 0.0249

GnomAD4 exome AF: 0.0202 AC: 4 AN: 198 Hom.: 0 Cov.: 0 AF XY: 0.0238 AC XY: 3 AN XY: 126

African (AFR) AF: 0.00 AC: 0 AN: 2

American (AMR) AF: 0.00 AC: 0 AN: 2

Ashkenazi Jewish (ASJ) AC: 0 AN: 0

East Asian (EAS) AF: 0.00 AC: 0 AN: 2

South Asian (SAS) AC: 0 AN: 0

European-Finnish (FIN) AF: 0.0181 AC: 3 AN: 166

Middle Eastern (MID) AF: 0.00 AC: 0 AN: 2

European-Non Finnish (NFE) AF: 0.0556 AC: 1 AN: 18

Other (OTH) AF: 0.00 AC: 0 AN: 6

GnomAD4 genome AF: 0.0213 AC: 3242 AN: 152298 Hom.: 42 Cov.: 32 AF XY: 0.0202 AC XY: 1507 AN XY: 74468

African (AFR) AF: 0.00503 AC: 209 AN: 41550

American (AMR) AF: 0.0184 AC: 281 AN: 15298

Ashkenazi Jewish (ASJ) AF: 0.0115 AC: 40 AN: 3470

East Asian (EAS) AF: 0.00 AC: 0 AN: 5194

South Asian (SAS) AF: 0.00436 AC: 21 AN: 4822

European-Finnish (FIN) AF: 0.0287 AC: 305 AN: 10610

Middle Eastern (MID) AF: 0.00 AC: 0 AN: 294

European-Non Finnish (NFE) AF: 0.0339 AC: 2309 AN: 68034

Other (OTH) AF: 0.0246 AC: 52 AN: 2114

Alfa AF: 0.0284 Hom.: 10

Bravo AF: 0.0198

Asia WGS AF: 0.00260 AC: 9 AN: 3478

ClinVar

ClinVar submissions

Significance: Benign

Revision: criteria provided, multiple submitters, no conflicts

Pathogenic	VUS	Benign	Condition
-	-	1	not provided (1)
-	-	1	Retinitis pigmentosa (1)

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.80
CADD	Benign	4.7
DANN	Benign	0.67
PhyloP100		0.23
Mutation Taster		=100/0	polymorphism

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

Other links and lift over

dbSNP: rs1051718; hg19: chr14-24549611;