rs749663647

Variant summary

Our verdict is Uncertain significance. Variant got 3 ACMG points: 3P and 0B. PM2PP3

The NM_133452.3(RAVER1):​c.2173G>C​(p.Gly725Arg) variant causes a missense change. The variant allele was found at a frequency of 0.00000657 in 152,242 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a pathogenic outcome for this variant. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar. Another variant affecting the same amino acid position, but resulting in a different missense (i.e. G725S) has been classified as Uncertain significance.

Frequency

Genomes: š‘“ 0.0000066 ( 0 hom., cov: 32)

Consequence

RAVER1
NM_133452.3 missense

Scores

7
7
3

Clinical Significance

Not reported in ClinVar

Conservation

PhyloP100: 6.46
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]

Genome browser will be placed here

ACMG classification

Classification made for transcript

Verdict is Uncertain_significance. Variant got 3 ACMG points.

PM2
Very rare variant in population databases, with high coverage;
PP3
MetaRNN computational evidence supports a deleterious effect, 0.783

Transcripts

RefSeq

Gene Transcript HGVSc HGVSp Effect Exon rank MANE Protein UniProt
RAVER1NM_133452.3 linkc.2173G>C p.Gly725Arg missense_variant Exon 13 of 13 ENST00000617231.5 NP_597709.3 Q8IY67
RAVER1NM_001366174.1 linkc.2098G>C p.Gly700Arg missense_variant Exon 14 of 14 NP_001353103.1
RAVER1XM_047438143.1 linkc.1156G>C p.Gly386Arg missense_variant Exon 9 of 9 XP_047294099.1

Ensembl

Gene Transcript HGVSc HGVSp Effect Exon rank TSL MANE Protein Appris UniProt
RAVER1ENST00000617231.5 linkc.2173G>C p.Gly725Arg missense_variant Exon 13 of 13 5 NM_133452.3 ENSP00000482277.1 A0A087WZ13
ENSG00000267303ENST00000586529.1 linkn.427G>C non_coding_transcript_exon_variant Exon 5 of 8 5 ENSP00000467814.1 K7EQG2
RAVER1ENST00000592208.5 linkn.3407G>C non_coding_transcript_exon_variant Exon 10 of 10 1

Frequencies

GnomAD3 genomes
AF:
0.00000657
AC:
1
AN:
152242
Hom.:
0
Cov.:
32
show subpopulations
Gnomad AFR
AF:
0.00
Gnomad AMI
AF:
0.00
Gnomad AMR
AF:
0.00
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:
0.0000147
Gnomad OTH
AF:
0.00
GnomAD4 exome
Cov.:
31
GnomAD4 genome
AF:
0.00000657
AC:
1
AN:
152242
Hom.:
0
Cov.:
32
AF XY:
0.00
AC XY:
0
AN XY:
74380
show subpopulations
Gnomad4 AFR
AF:
0.00
Gnomad4 AMR
AF:
0.00
Gnomad4 ASJ
AF:
0.00
Gnomad4 EAS
AF:
0.00
Gnomad4 SAS
AF:
0.00
Gnomad4 FIN
AF:
0.00
Gnomad4 NFE
AF:
0.0000147
Gnomad4 OTH
AF:
0.00
Bravo
AF:
0.00000378

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name
Calibrated prediction
Score
Prediction
BayesDel_addAF
Pathogenic
0.26
D
BayesDel_noAF
Uncertain
0.13
CADD
Pathogenic
27
DANN
Pathogenic
1.0
DEOGEN2
Benign
0.098
.;T;T
Eigen
Uncertain
0.66
Eigen_PC
Uncertain
0.61
FATHMM_MKL
Pathogenic
0.97
D
LIST_S2
Pathogenic
0.99
D;.;D
M_CAP
Uncertain
0.096
D
MetaRNN
Pathogenic
0.78
D;D;D
MetaSVM
Benign
-0.65
T
PrimateAI
Pathogenic
0.87
D
PROVEAN
Uncertain
-3.4
.;D;.
REVEL
Uncertain
0.37
Sift
Pathogenic
0.0
.;D;.
Sift4G
Uncertain
0.0080
D;D;D
Polyphen
1.0
.;D;D
Vest4
0.91
MutPred
0.43
.;Gain of MoRF binding (P = 0.0146);Gain of MoRF binding (P = 0.0146);
MVP
0.55
MPC
0.61
ClinPred
0.99
D
GERP RS
5.0
gMVP
0.78

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.

Other links and lift over

dbSNP: rs749663647; hg19: chr19-10428177; API