rs17023218

Variant names:

• chr3-29301226-C-A
• rs17023218
• NM_001003793.3:c.75+19470C>A

Variant summary

Our verdict is Benign. The variant received -12 ACMG points: 0P and 12B. BP4_Strong BA1

The ENST00000383767.7(RBMS3):​c.75+19470C>A variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.206 in 151,776 control chromosomes in the GnomAD database, including 3,449 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 0.21 (3449 hom., cov: 32)
• Consequence: RBMS3 ENST00000383767.7 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -1.15
• Publications: 4 publications found

Genes affected

RBMS3 (HGNC:13427): (RNA binding motif single stranded interacting protein 3) This gene encodes an RNA-binding protein that belongs to the c-myc gene single-strand binding protein family. These proteins are characterized by the presence of two sets of ribonucleoprotein consensus sequence (RNP-CS) that contain conserved motifs, RNP1 and RNP2, originally described in RNA binding proteins, and required for DNA binding. These proteins have been implicated in such diverse functions as DNA replication, gene transcription, cell cycle progression and apoptosis. The encoded protein was isolated by virtue of its binding to an upstream element of the alpha2(I) collagen promoter. The observation that this protein localizes mostly in the cytoplasm suggests that it may be involved in a cytoplasmic function such as controlling RNA metabolism, rather than transcription. Multiple alternatively spliced transcript variants encoding different isoforms have been found for this gene. [provided by RefSeq, Apr 2010]

ENSG00000283563 (HGNC:):

ACMG classification

Our verdict: Benign. The variant received -12 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.71).
• BA1: GnomAd4 highest subpopulation (AMR) allele frequency at 95% confidence interval = 0.285 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
RBMS3	NM_001003793.3	c.75+19470C>A		intron_variant	Intron 1 of 14	ENST00000383767.7	NP_001003793.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
RBMS3	ENST00000383767.7	c.75+19470C>A		intron_variant	Intron 1 of 14	1	NM_001003793.3	ENSP00000373277.2
ENSG00000283563	ENST00000635992.1	n.*582+118097C>A		intron_variant	Intron 8 of 13	5		ENSP00000489994.1

Frequencies

GnomAD3 genomes AF: 0.205 AC: 31162 AN: 151658 Hom.: 3445 Cov.: 32

Gnomad AFR AF: 0.134

Gnomad AMI AF: 0.323

Gnomad AMR AF: 0.292

Gnomad ASJ AF: 0.195

Gnomad EAS AF: 0.186

Gnomad SAS AF: 0.206

Gnomad FIN AF: 0.222

Gnomad MID AF: 0.177

Gnomad NFE AF: 0.227

Gnomad OTH AF: 0.222

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

GnomAD4 genome AF: 0.206 AC: 31191 AN: 151776 Hom.: 3449 Cov.: 32 AF XY: 0.205 AC XY: 15226 AN XY: 74122

African (AFR) AF: 0.134 AC: 5556 AN: 41442

American (AMR) AF: 0.292 AC: 4449 AN: 15222

Ashkenazi Jewish (ASJ) AF: 0.195 AC: 675 AN: 3466

East Asian (EAS) AF: 0.187 AC: 959 AN: 5120

South Asian (SAS) AF: 0.209 AC: 1005 AN: 4820

European-Finnish (FIN) AF: 0.222 AC: 2335 AN: 10534

Middle Eastern (MID) AF: 0.184 AC: 54 AN: 294

European-Non Finnish (NFE) AF: 0.227 AC: 15398 AN: 67860

Other (OTH) AF: 0.221 AC: 465 AN: 2106

Alfa AF: 0.224 Hom.: 6373

Bravo AF: 0.209

Asia WGS AF: 0.184 AC: 638 AN: 3474

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.71
CADD	Benign	3.1
DANN	Benign	0.82
PhyloP100		-1.1
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: rs17023218; hg19: chr3-29342717;