NM_000326.5:c.700C>A

Variant names:

• chr15-89210794-G-T
• NM_000326.5:c.700C>A

Variant summary

Our verdict is Uncertain significance. Variant got 3 ACMG points: 3P and 0B. PM2 PP3

The NM_000326.5(RLBP1):​c.700C>A​(p.Arg234Arg) variant causes a synonymous change. The variant allele was found at a frequency of 0.000000696 in 1,436,926 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts 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: 7.0e-7 (0 hom.)
• Consequence: RLBP1 NM_000326.5 synonymous
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 4.29

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 3 ACMG points.

• PM2: Very rare variant in population databases, with high coverage
• PP3: Splicing scoreres supports a deletorius effect: Scorers claiming Pathogenic: max_spliceai. No scorers claiming Uncertain. No scorers claiming Benign.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
RLBP1	NM_000326.5	c.700C>A	p.Arg234Arg	synonymous_variant	Exon 8 of 9	ENST00000268125.10	NP_000317.1
RLBP1	XM_011521870.3	c.700C>A	p.Arg234Arg	synonymous_variant	Exon 8 of 9		XP_011520172.1
RLBP1	XM_047432927.1	c.700C>A	p.Arg234Arg	synonymous_variant	Exon 6 of 7		XP_047288883.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
RLBP1	ENST00000268125.10	c.700C>A	p.Arg234Arg	synonymous_variant	Exon 8 of 9	1	NM_000326.5	ENSP00000268125.5
RLBP1	ENST00000563254.1	c.100-30C>A		intron_variant	Intron 1 of 2	2		ENSP00000454740.1
RLBP1	ENST00000567787.1	n.*278C>A		non_coding_transcript_exon_variant	Exon 8 of 8	5		ENSP00000457251.1
RLBP1	ENST00000567787.1	n.*278C>A		3_prime_UTR_variant	Exon 8 of 8	5		ENSP00000457251.1

Frequencies

GnomAD3 genomes Cov.: 32

GnomAD4 exome AF: 6.96e-7 AC: 1 AN: 1436926 Hom.: 0 Cov.: 31 AF XY: 0.00000140 AC XY: 1 AN XY: 712326

Gnomad4 AFR exome AF: 0.00

Gnomad4 AMR exome AF: 0.00

Gnomad4 ASJ exome AF: 0.00

Gnomad4 EAS exome AF: 0.0000258

Gnomad4 SAS exome AF: 0.00

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
BayesDel_noAF	Benign	-0.36
CADD	Benign	22
DANN	Benign	0.68

Splicing

Name	Calibrated prediction	Score	Prediction
SpliceAI score (max)		0.70		Details are displayed if max score is > 0.2
DS_AG_spliceai		0.70		Position offset: -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: chr15-89754025;