rs1381392

chr3-28707823-G-A

Variant summary

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

The NR_038840.1(LINC00693):n.323-48935G>A variant causes a intron, non coding transcript 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: LINC00693 NR_038840.1 intron, non_coding_transcript
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 0.326

Genes affected

LINC00693 (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]

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 (SAS) allele frequency at 95% confidence interval = 0.226 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
LINC00693	NR_038840.1	n.323-48935G>A		intron_variant, non_coding_transcript_variant

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
RBMS3	ENST00000636680.2	c.213+131327G>A		intron_variant		5
RBMS3	ENST00000432518.6	n.810-48935G>A		intron_variant, non_coding_transcript_variant		5
RBMS3	ENST00000443912.5	n.87-28186G>A		intron_variant, non_coding_transcript_variant		4
RBMS3	ENST00000445077.1	n.70-49286G>A		intron_variant, non_coding_transcript_variant		3

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

Gnomad4 AFR AF: 0.0294

Gnomad4 AMR AF: 0.107

Gnomad4 ASJ AF: 0.211

Gnomad4 EAS AF: 0.0891

Gnomad4 SAS AF: 0.237

Gnomad4 FIN AF: 0.167

Gnomad4 NFE AF: 0.172

Gnomad4 OTH AF: 0.134

Alfa AF: 0.166 Hom.: 4151

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

Splicing

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

Publications

LitVar

Other links and lift over

dbSNP: rs1381392; hg19: chr3-28749314;