rs1219708248

Variant names:

• chr15-89210330-C-A
• NM_000326.5:c.909G>T

Your query was ambiguous. Multiple possible variants found:

• chr15-89210330-C-A
• chr15-89210330-C-T

Variant summary

Our verdict is Uncertain significance. Variant got 0 ACMG points: 2P and 2B. PM2 BP4_Moderate

The NM_000326.5(RLBP1):​c.909G>T​(p.Glu303Asp) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.000000684 in 1,461,878 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a benign outcome for this variant. 15/21 in silico tools predict a benign outcome for this variant. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar.

• Frequency:
  • Genomes: not found (cov: 32)
  • Exomes 𝑓: 6.8e-7 (0 hom.)
• Consequence: RLBP1 NM_000326.5 missense
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 0.893

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 Uncertain_significance. Variant got 0 ACMG points.

• PM2: Very rare variant in population databases, with high coverage
• BP4: Computational evidence support a benign effect (MetaRNN=0.1438925).

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
RLBP1	NM_000326.5	c.909G>T	p.Glu303Asp	missense_variant	Exon 9 of 9	ENST00000268125.10	NP_000317.1
RLBP1	XM_011521870.3	c.909G>T	p.Glu303Asp	missense_variant	Exon 9 of 9		XP_011520172.1
RLBP1	XM_047432927.1	c.909G>T	p.Glu303Asp	missense_variant	Exon 7 of 7		XP_047288883.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
RLBP1	ENST00000268125.10	c.909G>T	p.Glu303Asp	missense_variant	Exon 9 of 9	1	NM_000326.5	ENSP00000268125.5
RLBP1	ENST00000563254.1	c.279G>T	p.Glu93Asp	missense_variant	Exon 3 of 3	2		ENSP00000454740.1

Frequencies

GnomAD3 genomes Cov.: 32

GnomAD4 exome AF: 6.84e-7 AC: 1 AN: 1461878 Hom.: 0 Cov.: 32 AF XY: 0.00000138 AC XY: 1 AN XY: 727232

Gnomad4 AFR exome AF: 0.00

Gnomad4 AMR exome AF: 0.00

Gnomad4 ASJ exome AF: 0.00

Gnomad4 EAS exome AF: 0.00

Gnomad4 SAS exome AF: 0.00

Gnomad4 FIN exome AF: 0.00

Gnomad4 NFE exome AF: 8.99e-7

Gnomad4 OTH exome AF: 0.00

GnomAD4 genome Cov.: 32

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
AlphaMissense	Benign	0.15
BayesDel_addAF	Benign	-0.067	T
BayesDel_noAF	Benign	-0.33
CADD	Benign	15
DANN	Uncertain	0.99
DEOGEN2	Benign	0.34	T
Eigen	Benign	-0.71
Eigen_PC	Benign	-0.65
FATHMM_MKL	Uncertain	0.90	D
LIST_S2	Benign	0.81	T
M_CAP	Benign	0.030	D
MetaRNN	Benign	0.14	T
MetaSVM	Benign	-0.65	T
MutationAssessor	Benign	1.8	L
PrimateAI	Benign	0.35	T
PROVEAN	Benign	-1.1	N
REVEL	Benign	0.23
Sift	Benign	0.12	T
Sift4G	Benign	0.34	T
Polyphen		0.011	B
Vest4		0.084
MutPred		0.34		Loss of helix (P = 0.079);
MVP		0.64
MPC		0.20
ClinPred		0.29	T
GERP RS		-0.79
Varity_R		0.19
gMVP		0.78

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

No publications associated with this variant yet.

Other links and lift over

hg19: chr15-89753561;