rs7612518

Positions:

• chr3-28714628-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.323-42130G>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 0.448 in 151,948 control chromosomes in the GnomAD database, including 15,402 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 0.45 (15402 hom., cov: 31)
• Consequence: LINC00693 NR_038840.1 intron, non_coding_transcript
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 1.01

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=-0.89).
• BA1: GnomAd4 highest subpopulation (AMR) allele frequency at 95% confidence interval = 0.49 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
LINC00693	NR_038840.1	n.323-42130G>A		intron_variant, non_coding_transcript_variant

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
RBMS3	ENST00000636680.2	c.213+138132G>A		intron_variant		5		ENSP00000490271
RBMS3	ENST00000432518.6	n.810-42130G>A		intron_variant, non_coding_transcript_variant		5
RBMS3	ENST00000443912.5	n.87-21381G>A		intron_variant, non_coding_transcript_variant		4
RBMS3	ENST00000445077.1	n.70-42481G>A		intron_variant, non_coding_transcript_variant		3

Frequencies

GnomAD3 genomes AF: 0.448 AC: 68077 AN: 151828 Hom.: 15395 Cov.: 31

Gnomad AFR AF: 0.396

Gnomad AMI AF: 0.490

Gnomad AMR AF: 0.500

Gnomad ASJ AF: 0.463

Gnomad EAS AF: 0.435

Gnomad SAS AF: 0.330

Gnomad FIN AF: 0.483

Gnomad MID AF: 0.494

Gnomad NFE AF: 0.471

Gnomad OTH AF: 0.451

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

GnomAD4 genome AF: 0.448 AC: 68114 AN: 151948 Hom.: 15402 Cov.: 31 AF XY: 0.446 AC XY: 33159 AN XY: 74266

Gnomad4 AFR AF: 0.396

Gnomad4 AMR AF: 0.500

Gnomad4 ASJ AF: 0.463

Gnomad4 EAS AF: 0.436

Gnomad4 SAS AF: 0.330

Gnomad4 FIN AF: 0.483

Gnomad4 NFE AF: 0.471

Gnomad4 OTH AF: 0.447

Alfa AF: 0.474 Hom.: 2909

Bravo AF: 0.450

Asia WGS AF: 0.395 AC: 1376 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.89
CADD	Benign	12
DANN	Benign	0.68

Splicing

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

Publications

LitVar

Other links and lift over

dbSNP: rs7612518; hg19: chr3-28756119;