rs6549915

Variant names:

• chr3-29167660-T-C
• rs6549915
• ENST00000635992.1:n.*409-15296T>C

Variant summary

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

The ENST00000635992.1(ENSG00000283563):​n.*409-15296T>C variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.581 in 148,284 control chromosomes in the GnomAD database, including 26,815 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 0.58 (26815 hom., cov: 23)
• Consequence: ENSG00000283563 ENST00000635992.1 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -1.27
• Publications: 3 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]

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

ACMG classification

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

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-1.03).
• BA1: GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.769 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
ENSG00000283563	ENST00000635992.1	n.*409-15296T>C		intron_variant	Intron 7 of 13	5		ENSP00000489994.1

Frequencies

GnomAD3 genomes AF: 0.581 AC: 86136 AN: 148182 Hom.: 26785 Cov.: 23

Gnomad AFR AF: 0.776

Gnomad AMI AF: 0.658

Gnomad AMR AF: 0.415

Gnomad ASJ AF: 0.456

Gnomad EAS AF: 0.0854

Gnomad SAS AF: 0.510

Gnomad FIN AF: 0.466

Gnomad MID AF: 0.427

Gnomad NFE AF: 0.570

Gnomad OTH AF: 0.533

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

GnomAD4 genome AF: 0.581 AC: 86213 AN: 148284 Hom.: 26815 Cov.: 23 AF XY: 0.573 AC XY: 41379 AN XY: 72210

African (AFR) AF: 0.776 AC: 30970 AN: 39886

American (AMR) AF: 0.414 AC: 6191 AN: 14938

Ashkenazi Jewish (ASJ) AF: 0.456 AC: 1574 AN: 3452

East Asian (EAS) AF: 0.0856 AC: 434 AN: 5068

South Asian (SAS) AF: 0.511 AC: 2364 AN: 4630

European-Finnish (FIN) AF: 0.466 AC: 4560 AN: 9790

Middle Eastern (MID) AF: 0.428 AC: 125 AN: 292

European-Non Finnish (NFE) AF: 0.570 AC: 38325 AN: 67284

Other (OTH) AF: 0.527 AC: 1078 AN: 2044

Alfa AF: 0.850 Hom.: 19158

Bravo AF: 0.584

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-1.0
CADD	Benign	1.1
DANN	Benign	0.32
PhyloP100		-1.3

Splicing

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

Other links and lift over

dbSNP: rs6549915; hg19: chr3-29209151;