Genetic Variant RLBP1:c.*322C>T (chr15-89209963-G-A) – ACMG Classification: Benign (-20 pts)

Variant summary

Our verdict is Benign. Variant got -20 ACMG points: 0P and 20B. BP4_StrongBP6_Very_StrongBA1

The NM_000326.5(RLBP1):c.*322C>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 0.0182 in 392,554 control chromosomes in the GnomAD database, including 437 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★★).

Frequency

Genomes: 𝑓 0.038 ( 372 hom., cov: 32)

Exomes 𝑓: 0.0058 ( 65 hom. )

Consequence

RLBP1
NM_000326.5 3_prime_UTR

Scores

Clinical Significance

Benign criteria provided, multiple submitters, no conflicts B:4

Conservation

PhyloP100: -0.0720

Variant links:

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 links:

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ACMG classification

Classification made for transcript

Verdict is Benign. Variant got -20 ACMG points.

BP4

Computational evidence support a benign effect (BayesDel_noAF=-0.87).

BP6

Variant 15-89209963-G-A is Benign according to our data. Variant chr15-89209963-G-A is described in ClinVar as [Benign]. Clinvar id is 317227.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars.

BA1

GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.126 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	Effect	Exon rank	MANE	Protein	UniProt
RLBP1	NM_000326.5 link	c.*322C>T	3_prime_UTR_variant	Exon 9 of 9	ENST00000268125.10	NP_000317.1	P12271
RLBP1	XM_011521870.3 link	c.*322C>T	3_prime_UTR_variant	Exon 9 of 9		XP_011520172.1	P12271
RLBP1	XM_047432927.1 link	c.*322C>T	3_prime_UTR_variant	Exon 7 of 7		XP_047288883.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
RLBP1	ENST00000268125 link	c.*322C>T		3_prime_UTR_variant	Exon 9 of 9	1	NM_000326.5	ENSP00000268125.5		P12271
RLBP1	ENST00000563254.1 link	c.*322C>T		downstream_gene_variant		2		ENSP00000454740.1		H3BN92

Frequencies

GnomAD3 genomes

AF:

0.0378

AC:

5755

AN:

152188

Hom.:

372

Cov.:

show subpopulations

Gnomad AFR

AF:

0.129

Gnomad AMI

AF:

0.00

Gnomad AMR

AF:

0.0160

Gnomad ASJ

AF:

0.00

Gnomad EAS

AF:

0.00

Gnomad SAS

AF:

0.00124

Gnomad FIN

AF:

0.00

Gnomad MID

AF:

0.0190

Gnomad NFE

AF:

0.00104

Gnomad OTH

AF:

0.0320

GnomAD4 exome

AF:

0.00577

AC:

1386

AN:

240248

Hom.:

Cov.:

AF XY:

0.00513

AC XY:

651

AN XY:

126854

show subpopulations

Gnomad4 AFR exome

AF:

0.129

Gnomad4 AMR exome

AF:

0.0104

Gnomad4 ASJ exome

AF:

0.00

Gnomad4 EAS exome

AF:

0.0000771

Gnomad4 SAS exome

AF:

0.000669

Gnomad4 FIN exome

AF:

0.00

Gnomad4 NFE exome

AF:

0.000849

Gnomad4 OTH exome

AF:

0.0102

GnomAD4 genome

AF:

0.0379

AC:

5769

AN:

152306

Hom.:

372

Cov.:

AF XY:

0.0364

AC XY:

2709

AN XY:

74480

show subpopulations

Gnomad4 AFR

AF:

0.129

Gnomad4 AMR

AF:

0.0159

Gnomad4 ASJ

AF:

0.00

Gnomad4 EAS

AF:

0.00

Gnomad4 SAS

AF:

0.00124

Gnomad4 FIN

AF:

0.00

Gnomad4 NFE

AF:

0.00104

Gnomad4 OTH

AF:

0.0322

Alfa

AF:

0.00960

Hom.:

Bravo

AF:

0.0430

Asia WGS

AF:

0.0130

AC:

AN:

3478

ClinVar

Significance: Benign

Submissions summary: Benign:4

Revision: criteria provided, multiple submitters, no conflicts

LINK: link

Submissions by phenotype

Pigmentary retinal dystrophy

Benign:1

Apr 13, 2018

Illumina Laboratory Services, Illumina

Significance: Benign

Review Status: criteria provided, single submitter

Collection Method: clinical testing

This variant was observed as part of a predisposition screen in an ostensibly healthy population. A literature search was performed for the gene, cDNA change, and amino acid change (where applicable). No publications were found based on this search. Allele frequency data from public databases was too high to be consistent with this variant causing disease. Therefore, this variant is classified as benign. -

Newfoundland cone-rod dystrophy

Benign:1

Apr 13, 2018

Illumina Laboratory Services, Illumina

Significance: Benign

Review Status: criteria provided, single submitter

Collection Method: clinical testing

not provided

Benign:1

Breakthrough Genomics, Breakthrough Genomics

Significance: Benign

Review Status: criteria provided, single submitter

Collection Method: not provided

- -

Retinitis pigmentosa

Benign:1

Apr 13, 2018

Illumina Laboratory Services, Illumina

Significance: Benign

Review Status: criteria provided, single submitter

Collection Method: clinical testing

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

BayesDel_noAF

Benign

-0.87

CADD

Benign

4.7

DANN

Benign

0.71

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

Publications

LitVar

Below is the list of publications found by LitVar. It may be empty.

Variant summary

Frequency

Consequence

Scores

Clinical Significance

Conservation

ACMG classification

Transcripts

RefSeq

Ensembl

Frequencies

ClinVar

Submissions by phenotype

Computational scores

Splicing

Publications

LitVar

Other links and lift over