rs17023218

chr3-29301226-C-A

Variant summary

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

The NM_001003793.3(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 NM_001003793.3 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -1.15

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]

ACMG classification

Verdict is Benign. Variant got -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/exons	MANE	UniProt
RBMS3	NM_001003793.3	c.75+19470C>A		intron_variant		ENST00000383767.7

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
RBMS3	ENST00000383767.7	c.75+19470C>A		intron_variant		1	NM_001003793.3

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

Gnomad4 AFR AF: 0.134

Gnomad4 AMR AF: 0.292

Gnomad4 ASJ AF: 0.195

Gnomad4 EAS AF: 0.187

Gnomad4 SAS AF: 0.209

Gnomad4 FIN AF: 0.222

Gnomad4 NFE AF: 0.227

Gnomad4 OTH AF: 0.221

Alfa AF: 0.225 Hom.: 5463

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

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: rs17023218; hg19: chr3-29342717;