rs2218724

Variant names:

• chr3-29884027-A-G
• rs2218724
• NM_001003793.3:c.745-135A>G

Variant summary

Our verdict is Benign. The variant received -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
• Publications: 3 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]

ACMG classification

Our verdict: Benign. The variant received -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.

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_001003793.3. You can select a different transcript below to see updated ACMG assignments.

RefSeq Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	RBMS3	NM_001003793.3	MANE Select	c.745-135A>G		intron	N/A	NP_001003793.1	Q6XE24-1
	RBMS3	NM_001330696.1		c.742-135A>G		intron	N/A	NP_001317625.1	C9JIJ9
	RBMS3	NM_001177712.2		c.784-135A>G		intron	N/A	NP_001171183.1	Q6XE24-2

Ensembl Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	RBMS3	ENST00000383767.7	TSL:1 MANE Select	c.745-135A>G		intron	N/A	ENSP00000373277.2	Q6XE24-1
	RBMS3	ENST00000456853.1	TSL:1	c.784-135A>G		intron	N/A	ENSP00000400519.1	Q6XE24-2
	RBMS3	ENST00000273139.13	TSL:1	c.745-135A>G		intron	N/A	ENSP00000273139.9	Q6XE24-4

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

African (AFR) AF: 0.514 AC: 7129 AN: 13880

American (AMR) AF: 0.375 AC: 7052 AN: 18806

Ashkenazi Jewish (ASJ) AF: 0.292 AC: 4105 AN: 14042

East Asian (EAS) AF: 0.182 AC: 5666 AN: 31164

South Asian (SAS) AF: 0.320 AC: 14095 AN: 44082

European-Finnish (FIN) AF: 0.389 AC: 15352 AN: 39416

Middle Eastern (MID) AF: 0.271 AC: 994 AN: 3672

European-Non Finnish (NFE) AF: 0.341 AC: 120499 AN: 353580

Other (OTH) AF: 0.339 AC: 9608 AN: 28362

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

African (AFR) AF: 0.513 AC: 21236 AN: 41414

American (AMR) AF: 0.359 AC: 5467 AN: 15232

Ashkenazi Jewish (ASJ) AF: 0.287 AC: 991 AN: 3454

East Asian (EAS) AF: 0.176 AC: 907 AN: 5140

South Asian (SAS) AF: 0.330 AC: 1588 AN: 4808

European-Finnish (FIN) AF: 0.385 AC: 4065 AN: 10564

Middle Eastern (MID) AF: 0.289 AC: 85 AN: 294

European-Non Finnish (NFE) AF: 0.343 AC: 23289 AN: 67878

Other (OTH) AF: 0.350 AC: 739 AN: 2110

Alfa AF: 0.351 Hom.: 40168

Bravo AF: 0.393

Asia WGS AF: 0.276 AC: 962 AN: 3476

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.93
CADD	Benign	0.58
DANN	Benign	0.34
PhyloP100		-1.2
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: rs2218724; hg19: chr3-29925518; COSMIC: COSV56136972;