15-89209989-C-T

Position:

• chr15-89209989-C-T

Variant summary

Our verdict is Benign. Variant got -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

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]

ACMG classification

Verdict is Benign. Variant got -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 id 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.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
RLBP1	NM_000326.5	c.*296G>A		3_prime_UTR_variant	9/9	ENST00000268125.10	NP_000317.1
RLBP1	XM_011521870.3	c.*296G>A		3_prime_UTR_variant	9/9		XP_011520172.1
RLBP1	XM_047432927.1	c.*296G>A		3_prime_UTR_variant	7/7		XP_047288883.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
RLBP1	ENST00000268125	c.*296G>A		3_prime_UTR_variant	9/9	1	NM_000326.5	ENSP00000268125.5
RLBP1	ENST00000563254.1	c.*296G>A		downstream_gene_variant		2		ENSP00000454740.1

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

Gnomad4 AFR exome AF: 0.459

Gnomad4 AMR exome AF: 0.278

Gnomad4 ASJ exome AF: 0.332

Gnomad4 EAS exome AF: 0.191

Gnomad4 SAS exome AF: 0.362

Gnomad4 FIN exome AF: 0.425

Gnomad4 NFE exome AF: 0.390

Gnomad4 OTH exome AF: 0.372

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

Gnomad4 AFR AF: 0.464

Gnomad4 AMR AF: 0.293

Gnomad4 ASJ AF: 0.330

Gnomad4 EAS AF: 0.187

Gnomad4 SAS AF: 0.368

Gnomad4 FIN AF: 0.434

Gnomad4 NFE AF: 0.392

Gnomad4 OTH AF: 0.377

Alfa AF: 0.384 Hom.: 22976

Bravo AF: 0.385

Asia WGS AF: 0.307 AC: 1067 AN: 3478

ClinVar

Significance: Benign

Submissions summary: Benign:5

Revision: criteria provided, multiple submitters, no conflicts

Submissions by phenotype

not provided Benign:2

Benign, criteria provided, single submitter	not provided	Breakthrough Genomics, Breakthrough Genomics	-	- -
Benign, criteria provided, single submitter	clinical testing	GeneDx	May 14, 2021	- -

Pigmentary retinal dystrophy Benign:1

Benign, criteria provided, single submitter

clinical testing

Illumina Laboratory Services, Illumina

Jan 13, 2018

This variant was observed in the ICSL laboratory as part of a predisposition screen in an ostensibly healthy population. It had not been previously curated by ICSL or reported in the Human Gene Mutation Database (HGMD: prior to June 1st, 2018), and was therefore a candidate for classification through an automated scoring system. Utilizing variant allele frequency, disease prevalence and penetrance estimates, and inheritance mode, an automated score was calculated to assess if this variant is too frequent to cause the disease. Based on the score and internal cut-off values, a variant classified as benign is not then subjected to further curation. The score for this variant resulted in a classification of benign for this disease. -

Newfoundland cone-rod dystrophy Benign:1

Benign, criteria provided, single submitter

clinical testing

Illumina Laboratory Services, Illumina

Jan 13, 2018

This variant was observed in the ICSL laboratory as part of a predisposition screen in an ostensibly healthy population. It had not been previously curated by ICSL or reported in the Human Gene Mutation Database (HGMD: prior to June 1st, 2018), and was therefore a candidate for classification through an automated scoring system. Utilizing variant allele frequency, disease prevalence and penetrance estimates, and inheritance mode, an automated score was calculated to assess if this variant is too frequent to cause the disease. Based on the score and internal cut-off values, a variant classified as benign is not then subjected to further curation. The score for this variant resulted in a classification of benign for this disease. -

Retinitis pigmentosa Benign:1

Benign, criteria provided, single submitter

clinical testing

Illumina Laboratory Services, Illumina

Jan 13, 2018

This variant was observed in the ICSL laboratory as part of a predisposition screen in an ostensibly healthy population. It had not been previously curated by ICSL or reported in the Human Gene Mutation Database (HGMD: prior to June 1st, 2018), and was therefore a candidate for classification through an automated scoring system. Utilizing variant allele frequency, disease prevalence and penetrance estimates, and inheritance mode, an automated score was calculated to assess if this variant is too frequent to cause the disease. Based on the score and internal cut-off values, a variant classified as benign is not then subjected to further curation. The score for this variant resulted in a classification of benign for this disease. -

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.92
CADD	Benign	0.11
DANN	Benign	0.66

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

Publications

LitVar

Other links and lift over

dbSNP: rs2710; hg19: chr15-89753220;