15-89210118-A-C

Position:

• chr15-89210118-A-C

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.*167T>G variant causes a 3 prime UTR change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.881 in 719,514 control chromosomes in the GnomAD database, including 280,271 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★★).

• Frequency:
  • Genomes: 𝑓 0.89 (61141 hom., cov: 33)
  • Exomes 𝑓: 0.88 (219130 hom.)
• Consequence: RLBP1 NM_000326.5 3_prime_UTR
• Clinical Significance: Benign criteria provided, multiple submitters, no conflicts B:5
• Conservation: PhyloP100: -0.377

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=-0.88).
• BP6: Variant 15-89210118-A-C is Benign according to our data. Variant chr15-89210118-A-C is described in ClinVar as [Benign]. Clinvar id is 317230.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars.
• BA1: GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.975 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
RLBP1	NM_000326.5	c.*167T>G		3_prime_UTR_variant	9/9	ENST00000268125.10	NP_000317.1
RLBP1	XM_011521870.3	c.*167T>G		3_prime_UTR_variant	9/9		XP_011520172.1
RLBP1	XM_047432927.1	c.*167T>G		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.*167T>G		3_prime_UTR_variant	9/9	1	NM_000326.5	ENSP00000268125.5
RLBP1	ENST00000563254	c.*167T>G		3_prime_UTR_variant	3/3	2		ENSP00000454740.1

Frequencies

GnomAD3 genomes AF: 0.894 AC: 136067 AN: 152132 Hom.: 61083 Cov.: 33

Gnomad AFR AF: 0.955

Gnomad AMI AF: 0.906

Gnomad AMR AF: 0.899

Gnomad ASJ AF: 0.840

Gnomad EAS AF: 0.998

Gnomad SAS AF: 0.847

Gnomad FIN AF: 0.782

Gnomad MID AF: 0.867

Gnomad NFE AF: 0.872

Gnomad OTH AF: 0.892

GnomAD4 exome AF: 0.878 AC: 497890 AN: 567264 Hom.: 219130 Cov.: 7 AF XY: 0.875 AC XY: 263801 AN XY: 301490

Gnomad4 AFR exome AF: 0.952

Gnomad4 AMR exome AF: 0.917

Gnomad4 ASJ exome AF: 0.846

Gnomad4 EAS exome AF: 0.999

Gnomad4 SAS exome AF: 0.829

Gnomad4 FIN exome AF: 0.801

Gnomad4 NFE exome AF: 0.876

Gnomad4 OTH exome AF: 0.878

GnomAD4 genome AF: 0.894 AC: 136182 AN: 152250 Hom.: 61141 Cov.: 33 AF XY: 0.892 AC XY: 66352 AN XY: 74426

Gnomad4 AFR AF: 0.955

Gnomad4 AMR AF: 0.898

Gnomad4 ASJ AF: 0.840

Gnomad4 EAS AF: 0.998

Gnomad4 SAS AF: 0.846

Gnomad4 FIN AF: 0.782

Gnomad4 NFE AF: 0.872

Gnomad4 OTH AF: 0.894

Alfa AF: 0.888 Hom.: 7470

Bravo AF: 0.910

Asia WGS AF: 0.911 AC: 3169 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 12, 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 12, 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 12, 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	-0.88
CADD	Benign	0.78
DANN	Benign	0.44

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

Other links and lift over

dbSNP: rs834; hg19: chr15-89753349;