rs4680719

Positions:

• chr3-29234155-G-A

Variant summary

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

The ENST00000635992.1(ENSG00000283563):​n.*582+51026G>A variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.412 in 151,842 control chromosomes in the GnomAD database, including 13,219 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 0.41 (13219 hom., cov: 31)
• Consequence: ENSG00000283563 ENST00000635992.1 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.471

Genes affected

ENSG00000283563 (HGNC:):

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-AS3 (HGNC:39989): (RBMS3 antisense RNA 3)

ACMG classification

Verdict is Benign. Variant got -12 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.98).
• BA1: GnomAd4 highest subpopulation (AMR) allele frequency at 95% confidence interval = 0.501 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
ENSG00000283563	ENST00000635992.1	n.*582+51026G>A		intron_variant		5		ENSP00000489994.1

Frequencies

GnomAD3 genomes AF: 0.412 AC: 62578 AN: 151726 Hom.: 13206 Cov.: 31

Gnomad AFR AF: 0.346

Gnomad AMI AF: 0.582

Gnomad AMR AF: 0.509

Gnomad ASJ AF: 0.453

Gnomad EAS AF: 0.259

Gnomad SAS AF: 0.403

Gnomad FIN AF: 0.405

Gnomad MID AF: 0.394

Gnomad NFE AF: 0.441

Gnomad OTH AF: 0.408

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

GnomAD4 genome AF: 0.412 AC: 62628 AN: 151842 Hom.: 13219 Cov.: 31 AF XY: 0.411 AC XY: 30510 AN XY: 74216

Gnomad4 AFR AF: 0.346

Gnomad4 AMR AF: 0.510

Gnomad4 ASJ AF: 0.453

Gnomad4 EAS AF: 0.258

Gnomad4 SAS AF: 0.404

Gnomad4 FIN AF: 0.405

Gnomad4 NFE AF: 0.441

Gnomad4 OTH AF: 0.407

Alfa AF: 0.428 Hom.: 3118

Bravo AF: 0.413

Asia WGS AF: 0.325 AC: 1127 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.98
CADD	Benign	1.3
DANN	Benign	0.56

Splicing

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

Publications

LitVar

Other links and lift over

dbSNP: rs4680719; hg19: chr3-29275646;