dbSNP rs577409503: RAVER1:p.Arg527Gln (chr19-10320845-C-T) – ACMG Classification: Likely_benign (-6 pts)

Variant summary

Our verdict is Likely benign. The variant received -6 ACMG points: 0P and 6B. BP4_ModerateBS2

The NM_133452.3(RAVER1):c.1580G>A(p.Arg527Gln) 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 1,511,976 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a benign outcome for this variant. 13/20 in silico tools predict a benign outcome for this variant. Variant has been reported in ClinVar as Uncertain significance (★).

Frequency

Genomes: 𝑓 0.0000066 ( 0 hom., cov: 32)

Exomes 𝑓: 0.000012 ( 0 hom. )

Consequence

RAVER1
NM_133452.3 missense

Scores

Clinical Significance

Uncertain significance criteria provided, single submitter U:1

Conservation

PhyloP100: 1.28

Publications

0 publications found

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 was made for transcript

Our verdict: Likely_benign. The variant received -6 ACMG points.

BP4

Computational evidence support a benign effect (MetaRNN=0.087512225).

BS2

High AC in GnomAdExome4 at 16 AD gene.

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_133452.3. You can select a different transcript below to see updated ACMG assignments.

RefSeq Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	RAVER1	NM_133452.3	MANE Select	c.1580G>A	p.Arg527Gln	missense	Exon 9 of 13	NP_597709.3	A0A087WZ13
	RAVER1	NM_001366174.1		c.1567+13G>A		intron	N/A	NP_001353103.1

Ensembl Transcripts

Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
RAVER1	ENST00000617231.5	TSL:5 MANE Select	c.1580G>A	p.Arg527Gln	missense	Exon 9 of 13	ENSP00000482277.1	A0A087WZ13
RAVER1	ENST00000592208.5	TSL:1	n.2814G>A		non_coding_transcript_exon	Exon 6 of 10
RAVER1	ENST00000910906.1		c.1655G>A	p.Arg552Gln	missense	Exon 10 of 14	ENSP00000580965.1

Frequencies

GnomAD3 genomes

AF:

0.00000658

AC:

AN:

152078

Hom.:

Cov.:

show subpopulations

Gnomad AFR

AF:

0.0000242

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:

0.00

Gnomad OTH

AF:

0.00

GnomAD2 exomes

AF:

0.0000359

AC:

AN:

139262

AF XY:

0.0000509

show subpopulations

Gnomad AFR exome

AF:

0.00

Gnomad AMR exome

AF:

0.000129

Gnomad ASJ exome

AF:

0.00

Gnomad EAS exome

AF:

0.00

Gnomad FIN exome

AF:

0.00

Gnomad NFE exome

AF:

0.0000448

Gnomad OTH exome

AF:

0.00

GnomAD4 exome

AF:

0.0000118

AC:

AN:

1359780

Hom.:

Cov.:

AF XY:

0.0000179

AC XY:

AN XY:

670784

show subpopulations

African (AFR)

AF:

0.0000359

AC:

AN:

27840

American (AMR)

AF:

0.000154

AC:

AN:

25976

Ashkenazi Jewish (ASJ)

AF:

0.00

AC:

AN:

20832

East Asian (EAS)

AF:

0.00

AC:

AN:

34346

South Asian (SAS)

AF:

0.00

AC:

AN:

71334

European-Finnish (FIN)

AF:

0.00

AC:

AN:

49226

Middle Eastern (MID)

AF:

0.00

AC:

AN:

5342

European-Non Finnish (NFE)

AF:

0.00000842

AC:

AN:

1069104

Other (OTH)

AF:

0.0000359

AC:

AN:

55780

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.475

Heterozygous variant carriers

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Exome Het

Variant carriers

<30

30-35

35-40

40-45

45-50

50-55

55-60

60-65

65-70

70-75

75-80

>80

Age

GnomAD4 genome

AF:

0.00000657

AC:

AN:

152196

Hom.:

Cov.:

AF XY:

0.0000134

AC XY:

AN XY:

74422

show subpopulations

African (AFR)

AF:

0.0000241

AC:

AN:

41508

American (AMR)

AF:

0.00

AC:

AN:

15302

Ashkenazi Jewish (ASJ)

AF:

0.00

AC:

AN:

3470

East Asian (EAS)

AF:

0.00

AC:

AN:

5162

South Asian (SAS)

AF:

0.00

AC:

AN:

4826

European-Finnish (FIN)

AF:

0.00

AC:

AN:

10616

Middle Eastern (MID)

AF:

0.00

AC:

AN:

294

European-Non Finnish (NFE)

AF:

0.00

AC:

AN:

67994

Other (OTH)

AF:

0.00

AC:

AN:

2112

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.625

Heterozygous variant carriers

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Alfa

AF:

0.00

Hom.:

Bravo

AF:

0.0000264

ExAC

AF:

0.0000335

AC:

ClinVar

ClinVar submissions

Significance:Uncertain significance

Revision:criteria provided, single submitter

View on ClinVar

Pathogenic

VUS

Benign

Condition

not specified (1)

Computational scores

Source: dbNSFP v4.9

Name

Calibrated prediction

Score

Prediction

AlphaMissense

Benign

0.14

BayesDel_addAF

Benign

-0.42

BayesDel_noAF

Benign

-0.61

CADD

Benign

(source)

DANN

Uncertain

1.0

DEOGEN2

Benign

0.0076

Eigen

Benign

-0.61

Eigen_PC

Benign

-0.44

FATHMM_MKL

Benign

0.34

LIST_S2

Benign

0.77

M_CAP

Benign

0.0090

MetaRNN

Benign

0.088

MetaSVM

Benign

-0.97

PhyloP100

1.3

PrimateAI

Uncertain

0.49

PROVEAN

Benign

0.030

REVEL

Benign

0.026

Sift

Benign

0.23

Sift4G

Benign

0.61

Polyphen

0.065

Vest4

0.32

MutPred

0.49

Loss of MoRF binding (P = 0.0186)

MVP

0.13

MPC

0.59

ClinPred

0.41

GERP RS

3.3

RBP_binding_hub_radar

0.0

RBP_regulation_power_radar

1.7

gMVP

0.28

Mutation Taster

=97/3

polymorphism

(source)

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

You must be logged in to view publications. This limit was set because tens of millions (!) of queries from AI bots are generated daily.

Variant summary

Frequency

Consequence

Scores

Clinical Significance

Conservation

Publications

ACMG classification

Variant Effect in Transcripts

RefSeq Transcripts

Ensembl Transcripts

Frequencies

Age Distribution

ClinVar

Computational scores

Splicing

Publications

Other links and lift over