chr15-89209989-C-T

Variant names:

• chr15-89209989-C-T
• rs2710
• NM_000326.5:c.*296G>A

Variant summary

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

The NM_000326.5(RLBP1):​c.*296G>A variant causes a 3 prime UTR change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.379 in 450,466 control chromosomes in the GnomAD database, including 33,582 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★★).

• Frequency:
  • Genomes: 𝑓 0.39 (12223 hom., cov: 33)
  • Exomes 𝑓: 0.37 (21359 hom.)
• Consequence: RLBP1 NM_000326.5 3_prime_UTR
• Clinical Significance: Benign criteria provided, multiple submitters, no conflicts B:5
• Conservation: PhyloP100: -1.76
• Publications: 17 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 -20 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.92).
• BP6: Variant 15-89209989-C-T is Benign according to our data. Variant chr15-89209989-C-T is described in ClinVar as Benign. ClinVar VariationId is 317228.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars.
• BA1: GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.459 is higher than 0.05.

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.*296G>A		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.*296G>A		3_prime_UTR	Exon 9 of 9	ENSP00000268125.5	P12271
	RLBP1	ENST00000873617.1		c.*296G>A		3_prime_UTR	Exon 9 of 9	ENSP00000543676.1
	RLBP1	ENST00000873618.1		c.*296G>A		3_prime_UTR	Exon 9 of 9	ENSP00000543677.1

Frequencies

GnomAD3 genomes AF: 0.394 AC: 59961 AN: 152026 Hom.: 12214 Cov.: 33

Gnomad AFR AF: 0.464

Gnomad AMI AF: 0.207

Gnomad AMR AF: 0.294

Gnomad ASJ AF: 0.330

Gnomad EAS AF: 0.186

Gnomad SAS AF: 0.368

Gnomad FIN AF: 0.434

Gnomad MID AF: 0.326

Gnomad NFE AF: 0.393

Gnomad OTH AF: 0.379

GnomAD4 exome AF: 0.370 AC: 110504 AN: 298322 Hom.: 21359 Cov.: 2 AF XY: 0.370 AC XY: 57781 AN XY: 155982

African (AFR) AF: 0.459 AC: 4310 AN: 9390

American (AMR) AF: 0.278 AC: 3684 AN: 13254

Ashkenazi Jewish (ASJ) AF: 0.332 AC: 3064 AN: 9218

East Asian (EAS) AF: 0.191 AC: 3493 AN: 18316

South Asian (SAS) AF: 0.362 AC: 13115 AN: 36244

European-Finnish (FIN) AF: 0.425 AC: 6808 AN: 16008

Middle Eastern (MID) AF: 0.353 AC: 467 AN: 1324

European-Non Finnish (NFE) AF: 0.390 AC: 69106 AN: 177220

Other (OTH) AF: 0.372 AC: 6457 AN: 17348

GnomAD4 genome AF: 0.394 AC: 59998 AN: 152144 Hom.: 12223 Cov.: 33 AF XY: 0.394 AC XY: 29265 AN XY: 74368

African (AFR) AF: 0.464 AC: 19264 AN: 41494

American (AMR) AF: 0.293 AC: 4486 AN: 15290

Ashkenazi Jewish (ASJ) AF: 0.330 AC: 1146 AN: 3470

East Asian (EAS) AF: 0.187 AC: 967 AN: 5182

South Asian (SAS) AF: 0.368 AC: 1777 AN: 4826

European-Finnish (FIN) AF: 0.434 AC: 4592 AN: 10572

Middle Eastern (MID) AF: 0.323 AC: 95 AN: 294

European-Non Finnish (NFE) AF: 0.392 AC: 26685 AN: 67988

Other (OTH) AF: 0.377 AC: 797 AN: 2116

Alfa AF: 0.386 Hom.: 48367

Bravo AF: 0.385

Asia WGS AF: 0.307 AC: 1067 AN: 3478

ClinVar

ClinVar submissions

Significance: Benign

Revision: criteria provided, multiple submitters, no conflicts

Pathogenic	VUS	Benign	Condition
-	-	2	not provided (2)
-	-	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	0.11
DANN	Benign	0.66
PhyloP100		-1.8
Mutation Taster		=100/0	polymorphism (auto)

Splicing

Name	Calibrated prediction	Score	Prediction
SpliceAI score (max)		0.010		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: rs2710; hg19: chr15-89753220;