rs1381392

Variant names:

• chr3-28707823-G-A
• rs1381392
• ENST00000635992.1:n.*339+131327G>A

Variant summary

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

The ENST00000635992.1(ENSG00000283563):​n.*339+131327G>A variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.126 in 152,180 control chromosomes in the GnomAD database, including 1,592 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 0.13 (1592 hom., cov: 32)
• Consequence: ENSG00000283563 ENST00000635992.1 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 0.326
• Publications: 13 publications found

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]

LINC00693 (HGNC:44526): (long intergenic non-protein coding RNA 693)

ACMG classification

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

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.9).
• BA1: GnomAd4 highest subpopulation (SAS) allele frequency at 95% confidence interval = 0.226 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
LINC00693	NR_038840.1	n.323-48935G>A		intron_variant	Intron 2 of 4

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
ENSG00000283563	ENST00000635992.1	n.*339+131327G>A		intron_variant	Intron 6 of 13	5		ENSP00000489994.1

Frequencies

GnomAD3 genomes AF: 0.126 AC: 19112 AN: 152062 Hom.: 1592 Cov.: 32

Gnomad AFR AF: 0.0295

Gnomad AMI AF: 0.157

Gnomad AMR AF: 0.107

Gnomad ASJ AF: 0.211

Gnomad EAS AF: 0.0889

Gnomad SAS AF: 0.238

Gnomad FIN AF: 0.167

Gnomad MID AF: 0.184

Gnomad NFE AF: 0.172

Gnomad OTH AF: 0.136

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

GnomAD4 genome AF: 0.126 AC: 19104 AN: 152180 Hom.: 1592 Cov.: 32 AF XY: 0.127 AC XY: 9418 AN XY: 74396

African (AFR) AF: 0.0294 AC: 1223 AN: 41550

American (AMR) AF: 0.107 AC: 1629 AN: 15276

Ashkenazi Jewish (ASJ) AF: 0.211 AC: 731 AN: 3470

East Asian (EAS) AF: 0.0891 AC: 460 AN: 5162

South Asian (SAS) AF: 0.237 AC: 1145 AN: 4824

European-Finnish (FIN) AF: 0.167 AC: 1769 AN: 10584

Middle Eastern (MID) AF: 0.180 AC: 53 AN: 294

European-Non Finnish (NFE) AF: 0.172 AC: 11667 AN: 67996

Other (OTH) AF: 0.134 AC: 284 AN: 2112

Alfa AF: 0.156 Hom.: 6029

Bravo AF: 0.115

Asia WGS AF: 0.124 AC: 433 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	3.8
DANN	Benign	0.79
PhyloP100		0.33

Splicing

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

Other links and lift over

dbSNP: rs1381392; hg19: chr3-28749314;