rs281423

Positions:

• chr19-10324817-T-C

Variant summary

Our verdict is Benign. Variant got -12 ACMG points: 0P and 12B. BP4_Strong BA1

The NM_133452.3(RAVER1):​c.757-1251A>G variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.838 in 152,148 control chromosomes in the GnomAD database, including 54,115 homozygotes. 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 0.84 (54115 hom., cov: 31)
• Consequence: RAVER1 NM_133452.3 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.495

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]

ACMG classification

Verdict is Benign. Variant got -12 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.95).
• BA1: GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.924 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
RAVER1	NM_133452.3	c.757-1251A>G		intron_variant		ENST00000617231.5
RAVER1	NM_001366174.1	c.757-1251A>G		intron_variant
RAVER1	XM_047438141.1	c.757-1251A>G		intron_variant
RAVER1	XM_047438142.1	c.757-1251A>G		intron_variant

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
RAVER1	ENST00000617231.5	c.757-1251A>G		intron_variant		5	NM_133452.3	P1
RAVER1	ENST00000592208.5	n.694-1251A>G		intron_variant, non_coding_transcript_variant		1
RAVER1	ENST00000591969.2	c.*392-1251A>G		intron_variant, NMD_transcript_variant		3

Frequencies

GnomAD3 genomes AF: 0.838 AC: 127451 AN: 152030 Hom.: 54072 Cov.: 31

Gnomad AFR AF: 0.932

Gnomad AMI AF: 0.719

Gnomad AMR AF: 0.795

Gnomad ASJ AF: 0.792

Gnomad EAS AF: 0.450

Gnomad SAS AF: 0.769

Gnomad FIN AF: 0.852

Gnomad MID AF: 0.858

Gnomad NFE AF: 0.828

Gnomad OTH AF: 0.838

We have no GnomAD4 exomes data on this position. Probably position not covered by the project.

GnomAD4 genome AF: 0.838 AC: 127544 AN: 152148 Hom.: 54115 Cov.: 31 AF XY: 0.835 AC XY: 62099 AN XY: 74372

Gnomad4 AFR AF: 0.932

Gnomad4 AMR AF: 0.794

Gnomad4 ASJ AF: 0.792

Gnomad4 EAS AF: 0.449

Gnomad4 SAS AF: 0.768

Gnomad4 FIN AF: 0.852

Gnomad4 NFE AF: 0.827

Gnomad4 OTH AF: 0.840

Alfa AF: 0.823 Hom.: 101998

Bravo AF: 0.838

Asia WGS AF: 0.705 AC: 2456 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.95
CADD	Benign	1.1
DANN	Benign	0.29
RBP_binding_hub_radar		0.0
RBP_regulation_power_radar		1.0

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: rs281423; hg19: chr19-10435493;