NM_001354768.3:c.*108C>T

Variant names:

• chr14-24081128-G-A
• rs552709917
• NM_001354768.3:c.*108C>T

Variant summary

Our verdict is Benign. The variant received -10 ACMG points: 0P and 10B. BP4_Strong BP6_Moderate BS1

The NM_001354768.3(NRL):​c.*108C>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 0.0000541 in 738,852 control chromosomes in the GnomAD database, including 1 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Likely benign (★).

• Frequency:
  • Genomes: 𝑓 0.00011 (1 hom., cov: 33)
  • Exomes 𝑓: 0.000039 (0 hom.)
• Consequence: NRL NM_001354768.3 3_prime_UTR
• Clinical Significance: Likely benign criteria provided, single submitter B:1
• Conservation: PhyloP100: -0.596
• Publications: 0 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 -10 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.67).
• BP6: Variant 14-24081128-G-A is Benign according to our data. Variant chr14-24081128-G-A is described in ClinVar as Likely_benign. ClinVar VariationId is 312939.Status of the report is criteria_provided_single_submitter, 1 stars.
• BS1: Variant frequency is greater than expected in population eas. GnomAd4 allele frequency = 0.000112 (17/152362) while in subpopulation EAS AF = 0.00328 (17/5190). AF 95% confidence interval is 0.00209. There are 1 homozygotes in GnomAd4. There are 11 alleles in the male GnomAd4 subpopulation. Median coverage is 33. This position passed quality control check.

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.*108C>T		3_prime_UTR	Exon 3 of 3	NP_001341697.1	P54845-1
	NRL	NM_001354769.1		c.*108C>T		3_prime_UTR	Exon 4 of 4	NP_001341698.1	P54845-1
	NRL	NM_006177.5		c.*108C>T		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.*108C>T		3_prime_UTR	Exon 3 of 3	ENSP00000454062.2	P54845-1
	NRL	ENST00000396997.1	TSL:1	c.*108C>T		3_prime_UTR	Exon 4 of 4	ENSP00000380193.1	P54845-1
	NRL	ENST00000397002.6	TSL:1	c.*108C>T		3_prime_UTR	Exon 3 of 3	ENSP00000380197.2	P54845-1

Frequencies

GnomAD3 genomes AF: 0.000112 AC: 17 AN: 152244 Hom.: 1 Cov.: 33

Gnomad AFR AF: 0.00

Gnomad AMI AF: 0.00

Gnomad AMR AF: 0.00

Gnomad ASJ AF: 0.00

Gnomad EAS AF: 0.00327

Gnomad SAS AF: 0.00

Gnomad FIN AF: 0.00

Gnomad MID AF: 0.00

Gnomad NFE AF: 0.00

Gnomad OTH AF: 0.00

GnomAD4 exome AF: 0.0000392 AC: 23 AN: 586490 Hom.: 0 Cov.: 8 AF XY: 0.0000277 AC XY: 8 AN XY: 288416

African (AFR) AF: 0.00 AC: 0 AN: 12900

American (AMR) AF: 0.00 AC: 0 AN: 8028

Ashkenazi Jewish (ASJ) AF: 0.00 AC: 0 AN: 11462

East Asian (EAS) AF: 0.000796 AC: 19 AN: 23880

South Asian (SAS) AF: 0.00 AC: 0 AN: 15596

European-Finnish (FIN) AF: 0.00 AC: 0 AN: 25050

Middle Eastern (MID) AF: 0.00 AC: 0 AN: 2902

European-Non Finnish (NFE) AF: 0.00000218 AC: 1 AN: 458870

Other (OTH) AF: 0.000108 AC: 3 AN: 27802

GnomAD4 genome AF: 0.000112 AC: 17 AN: 152362 Hom.: 1 Cov.: 33 AF XY: 0.000148 AC XY: 11 AN XY: 74504

African (AFR) AF: 0.00 AC: 0 AN: 41592

American (AMR) AF: 0.00 AC: 0 AN: 15312

Ashkenazi Jewish (ASJ) AF: 0.00 AC: 0 AN: 3470

East Asian (EAS) AF: 0.00328 AC: 17 AN: 5190

South Asian (SAS) AF: 0.00 AC: 0 AN: 4828

European-Finnish (FIN) AF: 0.00 AC: 0 AN: 10622

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

European-Non Finnish (NFE) AF: 0.00 AC: 0 AN: 68028

Other (OTH) AF: 0.00 AC: 0 AN: 2114

Alfa AF: 0.00 Hom.: 0

Bravo AF: 0.0000982

ClinVar

ClinVar submissions

Significance: Likely benign

Revision: criteria provided, single submitter

Pathogenic	VUS	Benign	Condition
-	-	1	Retinitis pigmentosa (1)

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.67
CADD	Benign	4.9
DANN	Benign	0.91
PhyloP100		-0.60

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: rs552709917; hg19: chr14-24550337;