15-89210314-G-C

Variant names:

• chr15-89210314-G-C
• NM_000326.5:c.925C>G

Variant summary

Our verdict is Likely benign. Variant got -2 ACMG points: 2P and 4B. PM2 BP4_Strong

The NM_000326.5(RLBP1):​c.925C>G​(p.Gln309Glu) 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 1,461,810 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: 1.54

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 Likely_benign. Variant got -2 ACMG points.

• PM2: Very rare variant in population databases, with high coverage
• BP4: Computational evidence support a benign effect (MetaRNN=0.054443628).

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
RLBP1	NM_000326.5	c.925C>G	p.Gln309Glu	missense_variant	Exon 9 of 9	ENST00000268125.10	NP_000317.1
RLBP1	XM_011521870.3	c.925C>G	p.Gln309Glu	missense_variant	Exon 9 of 9		XP_011520172.1
RLBP1	XM_047432927.1	c.925C>G	p.Gln309Glu	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.925C>G	p.Gln309Glu	missense_variant	Exon 9 of 9	1	NM_000326.5	ENSP00000268125.5
RLBP1	ENST00000563254.1	c.295C>G	p.Gln99Glu	missense_variant	Exon 3 of 3	2		ENSP00000454740.1

Frequencies

GnomAD3 genomes Cov.: 32

GnomAD4 exome AF: 6.84e-7 AC: 1 AN: 1461810 Hom.: 0 Cov.: 32 AF XY: 0.00000138 AC XY: 1 AN XY: 727212

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: 0.0000116

Gnomad4 FIN exome AF: 0.00

Gnomad4 NFE exome AF: 0.00

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	0.066
BayesDel_addAF	Benign	-0.13	T
BayesDel_noAF	Benign	-0.42
CADD	Benign	11
DANN	Benign	0.17
DEOGEN2	Benign	0.26	T
Eigen	Benign	-0.86
Eigen_PC	Benign	-0.70
FATHMM_MKL	Benign	0.43	N
LIST_S2	Benign	0.46	T
M_CAP	Benign	0.017	T
MetaRNN	Benign	0.054	T
MetaSVM	Benign	-1.0	T
MutationAssessor	Benign	-0.34	N
PrimateAI	Benign	0.26	T
PROVEAN	Benign	1.4	N
REVEL	Uncertain	0.29
Sift	Benign	0.54	T
Sift4G	Benign	0.46	T
Polyphen		0.0	B
Vest4		0.064
MutPred		0.50		Loss of helix (P = 0.079);
MVP		0.55
MPC		0.24
ClinPred		0.093	T
GERP RS		5.4
Varity_R		0.097
gMVP		0.35

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: chr15-89753545;