rs749663647

Variant names:

• chr19-10317501-C-G
• rs749663647
• NM_133452.3:c.2173G>C

Your query was ambiguous. Multiple possible variants found:

• chr19-10317501-C-G
• chr19-10317501-C-T

Variant summary

Our verdict is Uncertain significance. Variant got 3 ACMG points: 3P and 0B. PM2 PP3

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: 𝑓 0.0000066 (0 hom., cov: 32)
• Consequence: RAVER1 NM_133452.3 missense
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 6.46

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

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
RAVER1	NM_133452.3	c.2173G>C	p.Gly725Arg	missense_variant	Exon 13 of 13	ENST00000617231.5	NP_597709.3
RAVER1	NM_001366174.1	c.2098G>C	p.Gly700Arg	missense_variant	Exon 14 of 14		NP_001353103.1
RAVER1	XM_047438143.1	c.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
RAVER1	ENST00000617231.5	c.2173G>C	p.Gly725Arg	missense_variant	Exon 13 of 13	5	NM_133452.3	ENSP00000482277.1
ENSG00000267303	ENST00000586529.1	n.427G>C		non_coding_transcript_exon_variant	Exon 5 of 8	5		ENSP00000467814.1
RAVER1	ENST00000592208.5	n.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

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

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

Other links and lift over

dbSNP: rs749663647; hg19: chr19-10428177;