NM_000326.5:c.*380C>T

Variant names:

• chr15-89209905-G-A
• rs115275013
• NM_000326.5:c.*380C>T

Variant summary

Our verdict is Benign. The variant received -14 ACMG points: 0P and 14B. BP4_Strong BP6_Moderate BS1 BS2

The NM_000326.5(RLBP1):​c.*380C>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 0.00596 in 295,274 control chromosomes in the GnomAD database, including 36 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Likely benign (★).

• Frequency:
  • Genomes: 𝑓 0.010 (32 hom., cov: 32)
  • Exomes 𝑓: 0.0012 (4 hom.)
• Consequence: RLBP1 NM_000326.5 3_prime_UTR
• Clinical Significance: Benign/Likely benign criteria provided, single submitter B:3
• Conservation: PhyloP100: -0.347
• Publications: 0 publications found

Genes affected

RLBP1 (HGNC:10024): (retinaldehyde binding protein 1) The protein encoded by this gene is a 36-kD water-soluble protein which carries 11-cis-retinaldehyde or 11-cis-retinal as physiologic ligands. It may be a functional component of the visual cycle. Mutations of this gene have been associated with severe rod-cone dystrophy, Bothnia dystrophy (nonsyndromic autosomal recessive retinitis pigmentosa) and retinitis punctata albescens. [provided by RefSeq, Jul 2008]

RLBP1 Gene-Disease associations (from GenCC):

• Bothnia retinal dystrophy

  Inheritance: AR Classification: DEFINITIVE, STRONG, SUPPORTIVE Submitted by: Orphanet, G2P, Labcorp Genetics (formerly Invitae)
• RLBP1-related retinopathy

  Inheritance: AR Classification: DEFINITIVE Submitted by: ClinGen
• fundus albipunctatus

  Inheritance: AR, AD Classification: STRONG, SUPPORTIVE Submitted by: Labcorp Genetics (formerly Invitae), Orphanet
• Newfoundland cone-rod dystrophy

  Inheritance: AR Classification: STRONG Submitted by: Labcorp Genetics (formerly Invitae), G2P
• retinitis pigmentosa

  Inheritance: AD Classification: SUPPORTIVE Submitted by: Orphanet
• retinitis punctata albescens

  Inheritance: AD Classification: SUPPORTIVE Submitted by: Orphanet

ACMG classification

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

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.92).
• BP6: Variant 15-89209905-G-A is Benign according to our data. Variant chr15-89209905-G-A is described in ClinVar as Benign/Likely_benign. ClinVar VariationId is 317224.Status of the report is criteria_provided_single_submitter, 1 stars.
• BS1: Variant frequency is greater than expected in population afr. GnomAd4 allele frequency = 0.0105 (1591/152194) while in subpopulation AFR AF = 0.0356 (1477/41514). AF 95% confidence interval is 0.0341. There are 32 homozygotes in GnomAd4. There are 763 alleles in the male GnomAd4 subpopulation. Median coverage is 32. This position passed quality control check.
• BS2: High Homozygotes in GnomAd4 at 32 AR,AD gene

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_000326.5. 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
	RLBP1	NM_000326.5	MANE Select	c.*380C>T		3_prime_UTR	Exon 9 of 9	NP_000317.1	P12271

Ensembl Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	RLBP1	ENST00000268125.10	TSL:1 MANE Select	c.*380C>T		3_prime_UTR	Exon 9 of 9	ENSP00000268125.5	P12271
	RLBP1	ENST00000873617.1		c.*380C>T		3_prime_UTR	Exon 9 of 9	ENSP00000543676.1
	RLBP1	ENST00000873618.1		c.*380C>T		3_prime_UTR	Exon 9 of 9	ENSP00000543677.1

Frequencies

GnomAD3 genomes AF: 0.0104 AC: 1586 AN: 152076 Hom.: 32 Cov.: 32

Gnomad AFR AF: 0.0356

Gnomad AMI AF: 0.00

Gnomad AMR AF: 0.00563

Gnomad ASJ AF: 0.00

Gnomad EAS AF: 0.00

Gnomad SAS AF: 0.00

Gnomad FIN AF: 0.00

Gnomad MID AF: 0.00

Gnomad NFE AF: 0.0000882

Gnomad OTH AF: 0.0105

GnomAD4 exome AF: 0.00119 AC: 170 AN: 143080 Hom.: 4 Cov.: 0 AF XY: 0.000950 AC XY: 72 AN XY: 75812

African (AFR) AF: 0.0309 AC: 142 AN: 4592

American (AMR) AF: 0.00154 AC: 9 AN: 5828

Ashkenazi Jewish (ASJ) AF: 0.00 AC: 0 AN: 3662

East Asian (EAS) AF: 0.00 AC: 0 AN: 6636

South Asian (SAS) AF: 0.000133 AC: 3 AN: 22478

European-Finnish (FIN) AF: 0.00 AC: 0 AN: 6800

Middle Eastern (MID) AF: 0.00195 AC: 1 AN: 512

European-Non Finnish (NFE) AF: 0.0000470 AC: 4 AN: 85092

Other (OTH) AF: 0.00147 AC: 11 AN: 7480

GnomAD4 genome AF: 0.0105 AC: 1591 AN: 152194 Hom.: 32 Cov.: 32 AF XY: 0.0103 AC XY: 763 AN XY: 74404

African (AFR) AF: 0.0356 AC: 1477 AN: 41514

American (AMR) AF: 0.00563 AC: 86 AN: 15288

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

East Asian (EAS) AF: 0.00 AC: 0 AN: 5176

South Asian (SAS) AF: 0.00 AC: 0 AN: 4818

European-Finnish (FIN) AF: 0.00 AC: 0 AN: 10594

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

European-Non Finnish (NFE) AF: 0.0000882 AC: 6 AN: 68014

Other (OTH) AF: 0.0104 AC: 22 AN: 2114

Alfa AF: 0.00439 Hom.: 1

Bravo AF: 0.0114

Asia WGS AF: 0.00144 AC: 5 AN: 3478

ClinVar

ClinVar submissions

Significance: Benign/Likely benign

Revision: criteria provided, single submitter

Pathogenic	VUS	Benign	Condition
-	-	1	Newfoundland cone-rod dystrophy (1)
-	-	1	Pigmentary retinal dystrophy (1)
-	-	1	Retinitis pigmentosa (1)

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.92
CADD	Benign	0.25
DANN	Benign	0.54
PhyloP100		-0.35
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: rs115275013; hg19: chr15-89753136;