rs374391089

Variant names:

• chr19-10319173-C-A
• rs374391089
• NM_133452.3:c.1838G>T

Your query was ambiguous. Multiple possible variants found:

• chr19-10319173-C-A
• chr19-10319173-C-T

Variant summary

Our verdict is Uncertain significance. The variant received 1 ACMG points: 2P and 1B. PM2 BP4

The NM_133452.3(RAVER1):​c.1838G>T​(p.Arg613Leu) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.000000684 in 1,461,364 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Uncertain significance (★). Another variant affecting the same amino acid position, but resulting in a different missense (i.e. R613Q) has been classified as Uncertain significance.

• Frequency:
  • Genomes: not found (cov: 32)
  • Exomes 𝑓: 6.8e-7 (0 hom.)
• Consequence: RAVER1 NM_133452.3 missense
• Clinical Significance: Uncertain significance criteria provided, single submitter U:1
• Conservation: PhyloP100: 3.48
• Publications: 0 publications found

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]

ENSG00000267303 (HGNC:):

ACMG classification

Our verdict: Uncertain_significance. The variant received 1 ACMG points.

• PM2: Very rare variant in population databases, with high coverage
• BP4: Computational evidence support a benign effect (MetaRNN=0.40511942).

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.1838G>T	p.Arg613Leu	missense	Exon 10 of 13	NP_597709.3	A0A087WZ13
	RAVER1	NM_001366174.1		c.1763G>T	p.Arg588Leu	missense	Exon 11 of 14	NP_001353103.1

Ensembl Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	RAVER1	ENST00000617231.5	TSL:5 MANE Select	c.1838G>T	p.Arg613Leu	missense	Exon 10 of 13	ENSP00000482277.1	A0A087WZ13
	ENSG00000267303	ENST00000586529.1	TSL:5	n.92G>T		non_coding_transcript_exon	Exon 2 of 8	ENSP00000467814.1	K7EQG2
	RAVER1	ENST00000592208.5	TSL:1	n.3072G>T		non_coding_transcript_exon	Exon 7 of 10

Frequencies

GnomAD3 genomes Cov.: 32

GnomAD4 exome AF: 6.84e-7 AC: 1 AN: 1461364 Hom.: 0 Cov.: 30 AF XY: 0.00000138 AC XY: 1 AN XY: 726952

⚠️ The allele balance in gnomAD version 4 Exomes is significantly skewed from the expected value of 0.5.

African (AFR) AF: 0.00 AC: 0 AN: 33470

American (AMR) AF: 0.00 AC: 0 AN: 44708

Ashkenazi Jewish (ASJ) AF: 0.00 AC: 0 AN: 26128

East Asian (EAS) AF: 0.00 AC: 0 AN: 39686

South Asian (SAS) AF: 0.0000116 AC: 1 AN: 86224

European-Finnish (FIN) AF: 0.00 AC: 0 AN: 53356

Middle Eastern (MID) AF: 0.00 AC: 0 AN: 5766

European-Non Finnish (NFE) AF: 0.00 AC: 0 AN: 1111668

Other (OTH) AF: 0.00 AC: 0 AN: 60358

⚠️ The allele balance in gnomAD4 Exomes is highly skewed from 0.5 (p-value = 0), which strongly suggests a high chance of mosaicism in these individuals.

GnomAD4 genome Cov.: 32

ClinVar

ClinVar submissions

Significance: Uncertain significance

Revision: criteria provided, single submitter

Pathogenic	VUS	Benign	Condition
-	1	-	not specified (1)

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
AlphaMissense	Benign	0.27
BayesDel_addAF	Benign	-0.10	T
BayesDel_noAF	Benign	-0.39
CADD	Uncertain	24
DANN	Uncertain	1.0
DEOGEN2	Benign	0.019	T
Eigen	Uncertain	0.48
Eigen_PC	Uncertain	0.43
FATHMM_MKL	Uncertain	0.84	D
LIST_S2	Benign	0.85	T
M_CAP	Benign	0.017	T
MetaRNN	Benign	0.41	T
MetaSVM	Benign	-1.2	T
PhyloP100		3.5
PrimateAI	Uncertain	0.74	T
PROVEAN	Benign	-0.47	N
REVEL	Benign	0.11
Sift	Uncertain	0.013	D
Sift4G	Benign	0.25	T
Polyphen		0.99	D
Vest4		0.72
MutPred		0.23		Gain of glycosylation at K632 (P = 0.0849)
MVP		0.14
MPC		0.60
ClinPred		0.92	D
GERP RS		4.2
gMVP		0.51
Mutation Taster		=86/14	polymorphism

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

Other links and lift over

dbSNP: rs374391089; hg19: chr19-10429849;