rs2218724

Positions:

• chr3-29884027-A-G

Variant summary

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

The NM_001003793.3(RBMS3):​c.745-135A>G variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.348 in 698,810 control chromosomes in the GnomAD database, including 44,214 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 0.39 (12000 hom., cov: 32)
  • Exomes 𝑓: 0.34 (32214 hom.)
• Consequence: RBMS3 NM_001003793.3 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -1.22

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]

RBMS3 (HGNC:):

ACMG classification

Verdict is Benign. Variant got -12 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.93).
• BA1: GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.507 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
RBMS3	NM_001003793.3	c.745-135A>G		intron_variant		ENST00000383767.7	NP_001003793.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
RBMS3	ENST00000383767.7	c.745-135A>G		intron_variant		1	NM_001003793.3	ENSP00000373277.2

Frequencies

GnomAD3 genomes AF: 0.387 AC: 58715 AN: 151688 Hom.: 11972 Cov.: 32

Gnomad AFR AF: 0.512

Gnomad AMI AF: 0.466

Gnomad AMR AF: 0.359

Gnomad ASJ AF: 0.287

Gnomad EAS AF: 0.177

Gnomad SAS AF: 0.332

Gnomad FIN AF: 0.385

Gnomad MID AF: 0.275

Gnomad NFE AF: 0.343

Gnomad OTH AF: 0.353

GnomAD4 exome AF: 0.337 AC: 184500 AN: 547004 Hom.: 32214 AF XY: 0.335 AC XY: 95913 AN XY: 286206

Gnomad4 AFR exome AF: 0.514

Gnomad4 AMR exome AF: 0.375

Gnomad4 ASJ exome AF: 0.292

Gnomad4 EAS exome AF: 0.182

Gnomad4 SAS exome AF: 0.320

Gnomad4 FIN exome AF: 0.389

Gnomad4 NFE exome AF: 0.341

Gnomad4 OTH exome AF: 0.339

GnomAD4 genome AF: 0.387 AC: 58792 AN: 151806 Hom.: 12000 Cov.: 32 AF XY: 0.385 AC XY: 28556 AN XY: 74198

Gnomad4 AFR AF: 0.513

Gnomad4 AMR AF: 0.359

Gnomad4 ASJ AF: 0.287

Gnomad4 EAS AF: 0.176

Gnomad4 SAS AF: 0.330

Gnomad4 FIN AF: 0.385

Gnomad4 NFE AF: 0.343

Gnomad4 OTH AF: 0.350

Alfa AF: 0.342 Hom.: 18819

Bravo AF: 0.393

Asia WGS AF: 0.276 AC: 962 AN: 3476

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.93
CADD	Benign	0.58
DANN	Benign	0.34

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: rs2218724; hg19: chr3-29925518; COSMIC: COSV56136972;