10-47348472-C-T

Position:

• chr10-47348472-C-T

Variant summary

Our verdict is Benign. Variant got -20 ACMG points: 0P and 20B. BP4_Strong BP6_Very_Strong BA1

The NM_002900.3(RBP3):​c.-13C>T variant causes a 5 prime UTR change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0835 in 1,599,754 control chromosomes in the GnomAD database, including 6,521 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★★).

• Frequency:
  • Genomes: 𝑓 0.074 (557 hom., cov: 33)
  • Exomes 𝑓: 0.085 (5964 hom.)
• Consequence: RBP3 NM_002900.3 5_prime_UTR
• Clinical Significance: Benign criteria provided, multiple submitters, no conflicts B:3
• Conservation: PhyloP100: -0.346

Genes affected

RBP3 (HGNC:9921): (retinol binding protein 3) Interphotoreceptor retinol-binding protein is a large glycoprotein known to bind retinoids and found primarily in the interphotoreceptor matrix of the retina between the retinal pigment epithelium and the photoreceptor cells. It is thought to transport retinoids between the retinal pigment epithelium and the photoreceptors, a critical role in the visual process.The human IRBP gene is approximately 9.5 kbp in length and consists of four exons separated by three introns. The introns are 1.6-1.9 kbp long. The gene is transcribed by photoreceptor and retinoblastoma cells into an approximately 4.3-kilobase mRNA that is translated and processed into a glycosylated protein of 135,000 Da. The amino acid sequence of human IRBP can be divided into four contiguous homology domains with 33-38% identity, suggesting a series of gene duplication events. In the gene, the boundaries of these domains are not defined by exon-intron junctions, as might have been expected. The first three homology domains and part of the fourth are all encoded by the first large exon, which is 3,180 base pairs long. The remainder of the fourth domain is encoded in the last three exons, which are 191, 143, and approximately 740 base pairs long, respectively. [provided by RefSeq, Jul 2008]

ACMG classification

Verdict is Benign. Variant got -20 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.85).
• BP6: Variant 10-47348472-C-T is Benign according to our data. Variant chr10-47348472-C-T is described in ClinVar as [Benign]. Clinvar id is 299998.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars.
• BA1: GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.185 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
RBP3	NM_002900.3	c.-13C>T		5_prime_UTR_variant	1/4	ENST00000584701.2

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
RBP3	ENST00000584701.2	c.-13C>T		5_prime_UTR_variant	1/4	1	NM_002900.3	P1

Frequencies

GnomAD3 genomes AF: 0.0736 AC: 11198 AN: 152076 Hom.: 555 Cov.: 33

Gnomad AFR AF: 0.0305

Gnomad AMI AF: 0.122

Gnomad AMR AF: 0.0956

Gnomad ASJ AF: 0.0617

Gnomad EAS AF: 0.194

Gnomad SAS AF: 0.163

Gnomad FIN AF: 0.0739

Gnomad MID AF: 0.120

Gnomad NFE AF: 0.0791

Gnomad OTH AF: 0.0761

GnomAD3 exomes AF: 0.0982 AC: 23267 AN: 237010 Hom.: 1436 AF XY: 0.101 AC XY: 13139 AN XY: 129640

Gnomad AFR exome AF: 0.0289

Gnomad AMR exome AF: 0.116

Gnomad ASJ exome AF: 0.0624

Gnomad EAS exome AF: 0.207

Gnomad SAS exome AF: 0.160

Gnomad FIN exome AF: 0.0684

Gnomad NFE exome AF: 0.0747

Gnomad OTH exome AF: 0.0881

GnomAD4 exome AF: 0.0846 AC: 122414 AN: 1447560 Hom.: 5964 Cov.: 32 AF XY: 0.0870 AC XY: 62679 AN XY: 720446

Gnomad4 AFR exome AF: 0.0289

Gnomad4 AMR exome AF: 0.112

Gnomad4 ASJ exome AF: 0.0677

Gnomad4 EAS exome AF: 0.165

Gnomad4 SAS exome AF: 0.158

Gnomad4 FIN exome AF: 0.0683

Gnomad4 NFE exome AF: 0.0770

Gnomad4 OTH exome AF: 0.0916

GnomAD4 genome AF: 0.0736 AC: 11203 AN: 152194 Hom.: 557 Cov.: 33 AF XY: 0.0750 AC XY: 5580 AN XY: 74388

Gnomad4 AFR AF: 0.0305

Gnomad4 AMR AF: 0.0958

Gnomad4 ASJ AF: 0.0617

Gnomad4 EAS AF: 0.195

Gnomad4 SAS AF: 0.163

Gnomad4 FIN AF: 0.0739

Gnomad4 NFE AF: 0.0791

Gnomad4 OTH AF: 0.0777

Alfa AF: 0.0748 Hom.: 88

Bravo AF: 0.0709

Asia WGS AF: 0.165 AC: 570 AN: 3478

ClinVar

Significance: Benign

Submissions summary: Benign:3

Revision: criteria provided, multiple submitters, no conflicts

Submissions by phenotype

not provided Benign:1

Benign, criteria provided, single submitter

not provided

Breakthrough Genomics, Breakthrough Genomics

-

- -

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. -

Retinitis pigmentosa 66 Benign:1

Benign, criteria provided, single submitter

clinical testing

Genome-Nilou Lab

Nov 07, 2021

- -

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.85
CADD	Benign	3.4
DANN	Benign	0.58

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: rs41284964; hg19: chr10-48390890;