rs281423

Variant names:

• chr19-10324817-T-C
• rs281423
• NM_133452.3:c.757-1251A>G

Variant summary

Our verdict is Benign. The variant received -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
• Publications: 8 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]

ACMG classification

Our verdict: Benign. The variant received -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 rank	MANE	Protein	UniProt
RAVER1	NM_133452.3	c.757-1251A>G		intron_variant	Intron 3 of 12	ENST00000617231.5	NP_597709.3
RAVER1	NM_001366174.1	c.757-1251A>G		intron_variant	Intron 3 of 13		NP_001353103.1
RAVER1	XM_047438141.1	c.757-1251A>G		intron_variant	Intron 3 of 9		XP_047294097.1
RAVER1	XM_047438142.1	c.757-1251A>G		intron_variant	Intron 3 of 7		XP_047294098.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
RAVER1	ENST00000617231.5	c.757-1251A>G		intron_variant	Intron 3 of 12	5	NM_133452.3	ENSP00000482277.1
RAVER1	ENST00000592208.5	n.694-1251A>G		intron_variant	Intron 2 of 9	1
RAVER1	ENST00000591969.2	n.*392-1251A>G		intron_variant	Intron 3 of 3	3		ENSP00000465753.2

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

African (AFR) AF: 0.932 AC: 38691 AN: 41524

American (AMR) AF: 0.794 AC: 12123 AN: 15272

Ashkenazi Jewish (ASJ) AF: 0.792 AC: 2748 AN: 3468

East Asian (EAS) AF: 0.449 AC: 2319 AN: 5168

South Asian (SAS) AF: 0.768 AC: 3705 AN: 4822

European-Finnish (FIN) AF: 0.852 AC: 9020 AN: 10590

Middle Eastern (MID) AF: 0.854 AC: 251 AN: 294

European-Non Finnish (NFE) AF: 0.827 AC: 56263 AN: 67994

Other (OTH) AF: 0.840 AC: 1770 AN: 2106

Alfa AF: 0.825 Hom.: 230997

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
PhyloP100		-0.49
RBP_binding_hub_radar		0.0
RBP_regulation_power_radar		1.0
Mutation Taster		=100/0	polymorphism (auto)

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: rs281423; hg19: chr19-10435493;