15-89210118-A-T

Variant names:

• chr15-89210118-A-T
• rs834
• NM_000326.5:c.*167T>A

Variant summary

Our verdict is Likely benign. The variant received -2 ACMG points: 2P and 4B. PM2 BP4_Strong

The NM_000326.5(RLBP1):​c.*167T>A variant causes a 3 prime UTR change involving the alteration of a non-conserved nucleotide. The variant was absent in control chromosomes in GnomAD project. 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: 33)
  • Exomes 𝑓: 0.0 (0 hom.)
  • Failed GnomAD Quality Control
• Consequence: RLBP1 NM_000326.5 3_prime_UTR
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.377
• Publications: 10 publications found

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]

RLBP1 Gene-Disease associations (from GenCC):

• Bothnia retinal dystrophy

  Inheritance: AR Classification: DEFINITIVE, STRONG, SUPPORTIVE Submitted by: Orphanet, G2P, Labcorp Genetics (formerly Invitae)
• RLBP1-related retinopathy

  Inheritance: AR Classification: DEFINITIVE Submitted by: ClinGen
• fundus albipunctatus

  Inheritance: AR, AD Classification: STRONG, SUPPORTIVE Submitted by: Labcorp Genetics (formerly Invitae), Orphanet
• Newfoundland cone-rod dystrophy

  Inheritance: AR Classification: STRONG Submitted by: Labcorp Genetics (formerly Invitae), G2P
• retinitis pigmentosa

  Inheritance: AD Classification: SUPPORTIVE Submitted by: Orphanet
• retinitis punctata albescens

  Inheritance: AD Classification: SUPPORTIVE Submitted by: Orphanet

ACMG classification

Our verdict: Likely_benign. The variant received -2 ACMG points.

• PM2: Very rare variant in population databases, with high coverage
• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.85).

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_000326.5. You can select a different transcript below to see updated ACMG assignments.

RefSeq Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	RLBP1	NM_000326.5	MANE Select	c.*167T>A		3_prime_UTR	Exon 9 of 9	NP_000317.1	P12271

Ensembl Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	RLBP1	ENST00000268125.10	TSL:1 MANE Select	c.*167T>A		3_prime_UTR	Exon 9 of 9	ENSP00000268125.5	P12271
	RLBP1	ENST00000873617.1		c.*167T>A		3_prime_UTR	Exon 9 of 9	ENSP00000543676.1
	RLBP1	ENST00000873618.1		c.*167T>A		3_prime_UTR	Exon 9 of 9	ENSP00000543677.1

Frequencies

GnomAD3 genomes Cov.: 33

GnomAD4 exome Data not reliable, filtered out with message: AC0;AS_VQSR AF: 0.00 AC: 0 AN: 567564 Hom.: 0 Cov.: 7 AF XY: 0.00 AC XY: 0 AN XY: 301656

African (AFR) AF: 0.00 AC: 0 AN: 16158

American (AMR) AF: 0.00 AC: 0 AN: 29722

Ashkenazi Jewish (ASJ) AF: 0.00 AC: 0 AN: 17436

East Asian (EAS) AF: 0.00 AC: 0 AN: 33966

South Asian (SAS) AF: 0.00 AC: 0 AN: 57990

European-Finnish (FIN) AF: 0.00 AC: 0 AN: 34226

Middle Eastern (MID) AF: 0.00 AC: 0 AN: 2304

European-Non Finnish (NFE) AF: 0.00 AC: 0 AN: 345288

Other (OTH) AF: 0.00 AC: 0 AN: 30474

GnomAD4 genome Cov.: 33

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.85
CADD	Benign	0.74
DANN	Benign	0.31
PhyloP100		-0.38

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

Other links and lift over

dbSNP: rs834; hg19: chr15-89753349;