Variant 19-10317588-C-T details in Genebe, Genetics Data Aggregator

Variant summary

Our verdict is Benign. Variant got -8 ACMG points: 0P and 8B. BP4_StrongBS2

The NM_133452.3(RAVER1):c.2086G>A(p.Gly696Ser) variant causes a missense change. The variant allele was found at a frequency of 0.0000547 in 1,609,268 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 0.00017 ( 0 hom., cov: 32)

Exomes 𝑓: 0.000043 ( 0 hom. )

Consequence

RAVER1
NM_133452.3 missense

Scores

Clinical Significance

Uncertain significance criteria provided, single submitter U:1

Conservation

PhyloP100: 4.78

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 Benign. Variant got -8 ACMG points.

BP4

Computational evidence support a benign effect (MetaRNN=0.05695957).

BS2

High AC in GnomAd4 at 26 AD gene.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
RAVER1	NM_133452.3 linkuse as main transcript	c.2086G>A	p.Gly696Ser	missense_variant	13/13	ENST00000617231.5	NP_597709.3	Q8IY67
RAVER1	NM_001366174.1 linkuse as main transcript	c.2011G>A	p.Gly671Ser	missense_variant	14/14		NP_001353103.1
RAVER1	XM_047438143.1 linkuse as main transcript	c.1069G>A	p.Gly357Ser	missense_variant	9/9		XP_047294099.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	UniProt
RAVER1	ENST00000617231.5 linkuse as main transcript	c.2086G>A	p.Gly696Ser	missense_variant	13/13	5	NM_133452.3	ENSP00000482277.1	A0A087WZ13
ENSG00000267303	ENST00000586529.1 linkuse as main transcript	n.340G>A		non_coding_transcript_exon_variant	5/8	5		ENSP00000467814.1	K7EQG2
RAVER1	ENST00000592208.5 linkuse as main transcript	n.3320G>A		non_coding_transcript_exon_variant	10/10	1

Frequencies

GnomAD3 genomes

AF:

0.000171

AC:

AN:

152080

Hom.:

Cov.:

show subpopulations

Gnomad AFR

AF:

0.0000483

Gnomad AMI

AF:

0.00

Gnomad AMR

AF:

0.00118

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:

0.0000588

Gnomad OTH

AF:

0.000957

GnomAD3 exomes

AF:

0.0000919

AC:

AN:

239480

Hom.:

AF XY:

0.0000763

AC XY:

AN XY:

131098

show subpopulations

Gnomad AFR exome

AF:

0.0000680

Gnomad AMR exome

AF:

0.000449

Gnomad ASJ exome

AF:

0.00

Gnomad EAS exome

AF:

0.0000567

Gnomad SAS exome

AF:

0.00

Gnomad FIN exome

AF:

0.00

Gnomad NFE exome

AF:

0.0000468

Gnomad OTH exome

AF:

0.00

GnomAD4 exome

AF:

0.0000425

AC:

AN:

1457188

Hom.:

Cov.:

AF XY:

0.0000345

AC XY:

AN XY:

724902

show subpopulations

Gnomad4 AFR exome

AF:

0.0000600

Gnomad4 AMR exome

AF:

0.000341

Gnomad4 ASJ exome

AF:

0.00

Gnomad4 EAS exome

AF:

0.0000504

Gnomad4 SAS exome

AF:

0.00

Gnomad4 FIN exome

AF:

0.00

Gnomad4 NFE exome

AF:

0.0000324

Gnomad4 OTH exome

AF:

0.000116

GnomAD4 genome

AF:

0.000171

AC:

AN:

152080

Hom.:

Cov.:

AF XY:

0.000215

AC XY:

AN XY:

74306

show subpopulations

Gnomad4 AFR

AF:

0.0000483

Gnomad4 AMR

AF:

0.00118

Gnomad4 ASJ

AF:

0.00

Gnomad4 EAS

AF:

0.00

Gnomad4 SAS

AF:

0.00

Gnomad4 FIN

AF:

0.00

Gnomad4 NFE

AF:

0.0000588

Gnomad4 OTH

AF:

0.000957

Alfa

AF:

0.0000451

Hom.:

Bravo

AF:

0.000166

ESP6500AA

AF:

0.00

AC:

ESP6500EA

AF:

0.000122

AC:

ExAC

AF:

0.0000581

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

Nov 25, 2024

The c.2137G>A (p.G713S) alteration is located in exon 13 (coding exon 13) of the RAVER1 gene. This alteration results from a G to A substitution at nucleotide position 2137, causing the glycine (G) at amino acid position 713 to be replaced by a serine (S). 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

-0.40

BayesDel_noAF

Benign

-0.49

CADD

Pathogenic

DANN

Uncertain

1.0

DEOGEN2

Benign

0.010

.;T;T

Eigen

Uncertain

0.32

Eigen_PC

Uncertain

0.40

FATHMM_MKL

Uncertain

0.87

LIST_S2

Uncertain

0.88

D;.;D

M_CAP

Benign

0.0065

MetaRNN

Benign

0.057

T;T;T

MetaSVM

Benign

-0.98

PrimateAI

Uncertain

0.60

PROVEAN

Benign

0.25

.;N;.

REVEL

Benign

0.14

Sift

Benign

0.46

.;T;.

Sift4G

Benign

0.47

T;T;T

Polyphen

0.96

.;D;D

Vest4

0.11

MVP

0.21

MPC

0.35

ClinPred

0.11

GERP RS

5.2

RBP_binding_hub_radar

0.0

RBP_regulation_power_radar

1.1

gMVP

0.52

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