Genetic Variant RAVER1:p.Arg503Gln (chr19-10320917-C-T) – ACMG Classification: Likely_benign (-6 pts)

Variant summary

Our verdict is Likely benign. Variant got -6 ACMG points: 0P and 6B. BP4_ModerateBS2

The NM_133452.3(RAVER1):c.1508G>A(p.Arg503Gln) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0000104 in 1,348,460 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Uncertain significance (★).

Frequency

Genomes: not found (cov: 33)

Exomes 𝑓: 0.000010 ( 0 hom. )

Consequence

RAVER1
NM_133452.3 missense

Scores

Clinical Significance

Uncertain significance criteria provided, single submitter U:1

Conservation

PhyloP100: 2.03

Variant links:

Genes affected

RAVER1 (HGNC:30296): (ribonucleoprotein, PTB binding 1) Enables RNA binding activity. Predicted to be involved in regulation of alternative mRNA splicing, via spliceosome. Predicted to be located in cytoplasm. Predicted to be active in nucleus. [provided by Alliance of Genome Resources, Apr 2022]

RAVER1 links:

ENSG00000267303 (HGNC:):

ENSG00000267303 links:

Genome browser will be placed here

ACMG classification

Classification made for transcript

Verdict is Likely_benign. Variant got -6 ACMG points.

BP4

Computational evidence support a benign effect (MetaRNN=0.24949571).

BS2

High AC in GnomAdExome4 at 14 AD gene.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
RAVER1	NM_133452.3 link	c.1508G>A	p.Arg503Gln	missense_variant	Exon 9 of 13	ENST00000617231.5	NP_597709.3	Q8IY67

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
RAVER1	ENST00000617231.5 link	c.1508G>A	p.Arg503Gln	missense_variant	Exon 9 of 13	5	NM_133452.3	ENSP00000482277.1		A0A087WZ13
ENSG00000267303	ENST00000586529.1 link	n.-239G>A		upstream_gene_variant		5		ENSP00000467814.1		K7EQG2

Frequencies

GnomAD3 genomes

Cov.:

GnomAD3 exomes

AF:

0.00000693

AC:

AN:

144270

Hom.:

AF XY:

0.0000126

AC XY:

AN XY:

79218

show subpopulations

Gnomad AFR exome

AF:

0.00

Gnomad AMR exome

AF:

0.00

Gnomad ASJ exome

AF:

0.00

Gnomad EAS exome

AF:

0.00

Gnomad SAS exome

AF:

0.00

Gnomad FIN exome

AF:

0.00

Gnomad NFE exome

AF:

0.0000142

Gnomad OTH exome

AF:

0.00

GnomAD4 exome

AF:

0.0000104

AC:

AN:

1348460

Hom.:

Cov.:

AF XY:

0.0000106

AC XY:

AN XY:

662438

show subpopulations

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:

0.0000293

Gnomad4 FIN exome

AF:

0.00

Gnomad4 NFE exome

AF:

0.00000753

Gnomad4 OTH exome

AF:

0.0000724

GnomAD4 genome

Cov.:

ClinVar

Significance: Uncertain significance

Submissions summary: Uncertain:1

Revision: criteria provided, single submitter

LINK: link

Submissions by phenotype

not specified

Uncertain:1

Feb 07, 2025

Ambry Genetics

Significance: Uncertain significance

Review Status: criteria provided, single submitter

Collection Method: clinical testing

The c.1559G>A (p.R520Q) alteration is located in exon 9 (coding exon 9) of the RAVER1 gene. This alteration results from a G to A substitution at nucleotide position 1559, causing the arginine (R) at amino acid position 520 to be replaced by a glutamine (Q). Based on insufficient or conflicting evidence, the clinical significance of this alteration remains unclear. -

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

BayesDel_addAF

Uncertain

0.069

BayesDel_noAF

Benign

-0.14

CADD

Uncertain

DANN

Pathogenic

1.0

DEOGEN2

Benign

0.058

.;T;T

Eigen

Uncertain

0.32

Eigen_PC

Uncertain

0.31

FATHMM_MKL

Benign

0.65

LIST_S2

Uncertain

0.91

D;.;D

M_CAP

Benign

0.079

MetaRNN

Benign

0.25

T;T;T

MetaSVM

Uncertain

-0.23

PrimateAI

Uncertain

0.51

PROVEAN

Benign

-1.1

.;N;.

REVEL

Uncertain

0.45

Sift

Uncertain

0.013

.;D;.

Sift4G

Benign

0.20

T;T;T

Polyphen

0.98

.;D;D

Vest4

0.42

MutPred

0.32

.;Gain of relative solvent accessibility (P = 0.0249);Gain of relative solvent accessibility (P = 0.0249);

MVP

0.59

MPC

0.33

ClinPred

0.90

GERP RS

3.3

RBP_binding_hub_radar

0.0

RBP_regulation_power_radar

1.8

gMVP

0.24

Splicing

Name

Calibrated prediction

Score

Prediction

SpliceAI score (max)

0.010

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

Below is the list of publications found by LitVar. It may be empty.

Variant summary

Frequency

Consequence

Scores

Clinical Significance

Conservation

ACMG classification

Transcripts

RefSeq

Ensembl

Frequencies

ClinVar

Submissions by phenotype

Computational scores

Splicing

Publications

LitVar

Other links and lift over