rs10510615

chr3-28833769-T-Cchr3-28833769-T-G

Variant summary

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

The ENST00000636680.2(RBMS3):c.214-31455T>C variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0257 in 152,304 control chromosomes in the GnomAD database, including 100 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 0.026 (100 hom., cov: 32)
• Consequence: RBMS3 ENST00000636680.2 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.459

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=-0.9).
• BA1: GnomAd4 highest subpopulation (AMR) allele frequency at 95% confidence interval = 0.0602 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
RBMS3	ENST00000636680.2	c.214-31455T>C		intron_variant		5

Frequencies

GnomAD3 genomes AF: 0.0256 AC: 3898 AN: 152186 Hom.: 98 Cov.: 32

Gnomad AFR AF: 0.0307

Gnomad AMI AF: 0.00

Gnomad AMR AF: 0.0631

Gnomad ASJ AF: 0.0464

Gnomad EAS AF: 0.0615

Gnomad SAS AF: 0.0507

Gnomad FIN AF: 0.00433

Gnomad MID AF: 0.0223

Gnomad NFE AF: 0.0118

Gnomad OTH AF: 0.0368

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

GnomAD4 genome AF: 0.0257 AC: 3909 AN: 152304 Hom.: 100 Cov.: 32 AF XY: 0.0268 AC XY: 1997 AN XY: 74464

Gnomad4 AFR AF: 0.0307

Gnomad4 AMR AF: 0.0635

Gnomad4 ASJ AF: 0.0464

Gnomad4 EAS AF: 0.0617

Gnomad4 SAS AF: 0.0505

Gnomad4 FIN AF: 0.00433

Gnomad4 NFE AF: 0.0118

Gnomad4 OTH AF: 0.0388

Alfa AF: 0.0144 Hom.: 14

Bravo AF: 0.0297

Asia WGS AF: 0.0730 AC: 252 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.90
Cadd	Benign	0.76
Dann	Benign	0.48

Splicing

Find out detailed SpliceAI scores and Pangolin per-transcript scores at spliceailookup.broadinstitute.org

Publications

LitVar

Other links and lift over

dbSNP: rs10510615; hg19: chr3-28875260;