Variant 19-10318342-G-A details in Genebe, Genetics Data Aggregator

Variant summary

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

The NM_133452.3(RAVER1):c.1876C>T(p.Arg626Trp) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0000112 in 1,601,968 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: 𝑓 0.000033 ( 0 hom., cov: 32)

Exomes 𝑓: 0.0000090 ( 0 hom. )

Consequence

RAVER1
NM_133452.3 missense

Scores

Clinical Significance

Uncertain significance criteria provided, single submitter U:1

Conservation

PhyloP100: 3.53

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=0.22988498).

BS2

High AC in GnomAd4 at 5 AD gene.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
RAVER1	NM_133452.3 linkuse as main transcript	c.1876C>T	p.Arg626Trp	missense_variant	11/13	ENST00000617231.5	NP_597709.3	Q8IY67
RAVER1	NM_001366174.1 linkuse as main transcript	c.1801C>T	p.Arg601Trp	missense_variant	12/14		NP_001353103.1
RAVER1	XM_047438143.1 linkuse as main transcript	c.859C>T	p.Arg287Trp	missense_variant	7/9		XP_047294099.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
RAVER1	ENST00000617231.5 linkuse as main transcript	c.1876C>T	p.Arg626Trp	missense_variant	11/13	5	NM_133452.3	ENSP00000482277.1		A0A087WZ13
ENSG00000267303	ENST00000586529.1 linkuse as main transcript	n.130C>T		non_coding_transcript_exon_variant	3/8	5		ENSP00000467814.1		K7EQG2

Frequencies

GnomAD3 genomes

AF:

0.0000329

AC:

AN:

152188

Hom.:

Cov.:

show subpopulations

Gnomad AFR

AF:

0.00

Gnomad AMI

AF:

0.00

Gnomad AMR

AF:

0.000131

Gnomad ASJ

AF:

0.00

Gnomad EAS

AF:

0.00

Gnomad SAS

AF:

0.00

Gnomad FIN

AF:

0.00

Gnomad MID

AF:

0.00

Gnomad NFE

AF:

0.0000294

Gnomad OTH

AF:

0.000478

GnomAD4 exome

AF:

0.00000897

AC:

AN:

1449780

Hom.:

Cov.:

AF XY:

0.00000971

AC XY:

AN XY:

721214

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:

0.00

Gnomad4 FIN exome

AF:

0.00

Gnomad4 NFE exome

AF:

0.00000722

Gnomad4 OTH exome

AF:

0.0000836

GnomAD4 genome

AF:

0.0000329

AC:

AN:

152188

Hom.:

Cov.:

AF XY:

0.0000269

AC XY:

AN XY:

74340

show subpopulations

Gnomad4 AFR

AF:

0.00

Gnomad4 AMR

AF:

0.000131

Gnomad4 ASJ

AF:

0.00

Gnomad4 EAS

AF:

0.00

Gnomad4 SAS

AF:

0.00

Gnomad4 FIN

AF:

0.00

Gnomad4 NFE

AF:

0.0000294

Gnomad4 OTH

AF:

0.000478

Alfa

AF:

0.0000847

Hom.:

Bravo

AF:

0.0000718

ExAC

AF:

0.00000832

AC:

ClinVar

Significance: Uncertain significance

Submissions summary: Uncertain:1

Revision: criteria provided, single submitter

LINK: link

Submissions by phenotype

not specified

Uncertain:1

Uncertain significance, criteria provided, single submitter

clinical testing

Ambry Genetics

Oct 04, 2024

The c.1927C>T (p.R643W) alteration is located in exon 11 (coding exon 11) of the RAVER1 gene. This alteration results from a C to T substitution at nucleotide position 1927, causing the arginine (R) at amino acid position 643 to be replaced by a tryptophan (W). 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

Benign

-0.17

BayesDel_noAF

Benign

-0.48

CADD

Uncertain

DANN

Uncertain

1.0

DEOGEN2

Benign

0.024

.;T;T

Eigen

Uncertain

0.23

Eigen_PC

Benign

0.093

FATHMM_MKL

Uncertain

0.91

LIST_S2

Benign

0.74

T;.;T

M_CAP

Benign

0.021

MetaRNN

Benign

0.23

T;T;T

MetaSVM

Benign

-1.1

PrimateAI

Uncertain

0.71

PROVEAN

Benign

-1.1

.;N;.

REVEL

Benign

0.071

Sift

Uncertain

0.0070

.;D;.

Sift4G

Uncertain

0.037

D;D;D

Polyphen

1.0

.;D;D

Vest4

0.53

MVP

0.13

MPC

0.57

ClinPred

0.95

GERP RS

4.0

RBP_binding_hub_radar

0.0

RBP_regulation_power_radar

1.2

gMVP

0.54

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

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