rs1457644

Variant names:

• chr3-29631075-G-A
• rs1457644
• NM_001003793.3:c.399+43870G>A

Variant summary

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

The NM_001003793.3(RBMS3):​c.399+43870G>A variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0934 in 151,892 control chromosomes in the GnomAD database, including 1,183 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 0.093 (1183 hom., cov: 32)
• Consequence: RBMS3 NM_001003793.3 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.286
• Publications: 0 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:):

RBMS3-AS2 (HGNC:39988): (RBMS3 antisense RNA 2)

ACMG classification

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

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.95).
• BA1: GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.341 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
RBMS3	NM_001003793.3	c.399+43870G>A		intron_variant	Intron 4 of 14	ENST00000383767.7	NP_001003793.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
RBMS3	ENST00000383767.7	c.399+43870G>A		intron_variant	Intron 4 of 14	1	NM_001003793.3	ENSP00000373277.2
ENSG00000283563	ENST00000635992.1	n.*906+43870G>A		intron_variant	Intron 11 of 13	5		ENSP00000489994.1

Frequencies

GnomAD3 genomes AF: 0.0932 AC: 14147 AN: 151774 Hom.: 1177 Cov.: 32

Gnomad AFR AF: 0.176

Gnomad AMI AF: 0.0462

Gnomad AMR AF: 0.106

Gnomad ASJ AF: 0.0511

Gnomad EAS AF: 0.354

Gnomad SAS AF: 0.168

Gnomad FIN AF: 0.0135

Gnomad MID AF: 0.0475

Gnomad NFE AF: 0.0303

Gnomad OTH AF: 0.0885

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

GnomAD4 genome AF: 0.0934 AC: 14185 AN: 151892 Hom.: 1183 Cov.: 32 AF XY: 0.0970 AC XY: 7201 AN XY: 74248

African (AFR) AF: 0.177 AC: 7319 AN: 41454

American (AMR) AF: 0.106 AC: 1609 AN: 15196

Ashkenazi Jewish (ASJ) AF: 0.0511 AC: 177 AN: 3464

East Asian (EAS) AF: 0.354 AC: 1821 AN: 5142

South Asian (SAS) AF: 0.169 AC: 813 AN: 4824

European-Finnish (FIN) AF: 0.0135 AC: 143 AN: 10596

Middle Eastern (MID) AF: 0.0476 AC: 14 AN: 294

European-Non Finnish (NFE) AF: 0.0303 AC: 2056 AN: 67900

Other (OTH) AF: 0.0904 AC: 191 AN: 2112

Alfa AF: 0.0565 Hom.: 203

Bravo AF: 0.105

Asia WGS AF: 0.240 AC: 829 AN: 3470

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.95
CADD	Benign	1.1
DANN	Benign	0.59
PhyloP100		-0.29
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: rs1457644; hg19: chr3-29672566;