Variant 19-10317730-C-T details in Genebe, Genetics Data Aggregator

Variant summary

Our verdict is Likely benign. Variant got -4 ACMG points: 0P and 4B. BS2

The NM_133452.3(RAVER1):c.2033G>A(p.Gly678Asp) variant causes a missense change. The variant allele was found at a frequency of 0.0000964 in 1,596,868 control chromosomes in the GnomAD database, including 1 homozygotes. Variant has been reported in ClinVar as Uncertain significance (★).

Frequency

Genomes: 𝑓 0.000092 ( 0 hom., cov: 32)

Exomes 𝑓: 0.000097 ( 1 hom. )

Consequence

RAVER1
NM_133452.3 missense

Scores

Clinical Significance

Uncertain significance criteria provided, single submitter U:1

Conservation

PhyloP100: 3.77

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 -4 ACMG points.

BS2

High AC in GnomAd4 at 14 AD gene.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
RAVER1	NM_133452.3 linkuse as main transcript	c.2033G>A	p.Gly678Asp	missense_variant	12/13	ENST00000617231.5	NP_597709.3	Q8IY67
RAVER1	NM_001366174.1 linkuse as main transcript	c.1958G>A	p.Gly653Asp	missense_variant	13/14		NP_001353103.1
RAVER1	XM_047438143.1 linkuse as main transcript	c.1016G>A	p.Gly339Asp	missense_variant	8/9		XP_047294099.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	UniProt
RAVER1	ENST00000617231.5 linkuse as main transcript	c.2033G>A	p.Gly678Asp	missense_variant	12/13	5	NM_133452.3	ENSP00000482277.1	A0A087WZ13
ENSG00000267303	ENST00000586529.1 linkuse as main transcript	n.287G>A		non_coding_transcript_exon_variant	4/8	5		ENSP00000467814.1	K7EQG2
RAVER1	ENST00000592208.5 linkuse as main transcript	n.3267G>A		non_coding_transcript_exon_variant	9/10	1

Frequencies

GnomAD3 genomes

AF:

0.0000920

AC:

AN:

152196

Hom.:

Cov.:

show subpopulations

Gnomad AFR

AF:

0.00

Gnomad AMI

AF:

0.00

Gnomad AMR

AF:

0.000327

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:

0.000118

Gnomad OTH

AF:

0.000478

GnomAD3 exomes

AF:

0.000167

AC:

AN:

220902

Hom.:

AF XY:

0.000198

AC XY:

AN XY:

121292

show subpopulations

Gnomad AFR exome

AF:

0.00

Gnomad AMR exome

AF:

0.000403

Gnomad ASJ exome

AF:

0.00

Gnomad EAS exome

AF:

0.00

Gnomad SAS exome

AF:

0.0000363

Gnomad FIN exome

AF:

0.00

Gnomad NFE exome

AF:

0.000203

Gnomad OTH exome

AF:

0.000552

GnomAD4 exome

AF:

0.0000969

AC:

140

AN:

1444672

Hom.:

Cov.:

AF XY:

0.000102

AC XY:

AN XY:

717364

show subpopulations

Gnomad4 AFR exome

AF:

0.00

Gnomad4 AMR exome

AF:

0.000348

Gnomad4 ASJ exome

AF:

0.00

Gnomad4 EAS exome

AF:

0.00

Gnomad4 SAS exome

AF:

0.000143

Gnomad4 FIN exome

AF:

0.00

Gnomad4 NFE exome

AF:

0.0000923

Gnomad4 OTH exome

AF:

0.000151

GnomAD4 genome

AF:

0.0000920

AC:

AN:

152196

Hom.:

Cov.:

AF XY:

0.0000538

AC XY:

AN XY:

74328

show subpopulations

Gnomad4 AFR

AF:

0.00

Gnomad4 AMR

AF:

0.000327

Gnomad4 ASJ

AF:

0.00

Gnomad4 EAS

AF:

0.00

Gnomad4 SAS

AF:

0.00

Gnomad4 FIN

AF:

0.00

Gnomad4 NFE

AF:

0.000118

Gnomad4 OTH

AF:

0.000478

Alfa

AF:

0.000124

Hom.:

Bravo

AF:

0.000125

ExAC

AF:

0.000150

AC:

Asia WGS

AF:

0.000289

AC:

AN:

3478

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

Jun 21, 2023

The c.2084G>A (p.G695D) alteration is located in exon 12 (coding exon 12) of the RAVER1 gene. This alteration results from a G to A substitution at nucleotide position 2084, causing the glycine (G) at amino acid position 695 to be replaced by an aspartic acid (D). 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

AlphaMissense

Benign

0.26

BayesDel_addAF

Benign

-0.26

BayesDel_noAF

Benign

-0.29

CADD

Benign

DANN

Uncertain

1.0

DEOGEN2

Benign

0.025

.;T;T;T

Eigen

Uncertain

0.58

Eigen_PC

Uncertain

0.55

FATHMM_MKL

Uncertain

0.94

LIST_S2

Benign

0.80

T;.;T;T

M_CAP

Benign

0.030

MetaRNN

Uncertain

0.56

D;D;D;D

MetaSVM

Benign

-1.1

PrimateAI

Uncertain

0.73

PROVEAN

Benign

-0.80

.;N;.;.

REVEL

Benign

0.10

Sift

Uncertain

0.023

.;D;.;.

Sift4G

Benign

0.18

T;T;T;T

Polyphen

1.0, 1.0

.;D;D;D

Vest4

0.83

MVP

0.33

MPC

0.64

ClinPred

0.15

GERP RS

4.6

RBP_binding_hub_radar

0.0

RBP_regulation_power_radar

1.7

Varity_R

0.36

gMVP

0.51

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