chr3-28952016-C-T

Variant names:

• chr3-28952016-C-T
• rs6768946
• ENST00000635992.1:n.*408+86724C>T

Variant summary

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

The ENST00000635992.1(ENSG00000283563):​n.*408+86724C>T variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.515 in 151,912 control chromosomes in the GnomAD database, including 23,100 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 0.51 (23100 hom., cov: 32)
• Consequence: ENSG00000283563 ENST00000635992.1 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.828
• Publications: 4 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]

ACMG classification

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

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.71).
• BA1: GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.818 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.*408+86724C>T		intron_variant	Intron 7 of 13	5		ENSP00000489994.1

Frequencies

GnomAD3 genomes AF: 0.515 AC: 78183 AN: 151794 Hom.: 23106 Cov.: 32

Gnomad AFR AF: 0.211

Gnomad AMI AF: 0.519

Gnomad AMR AF: 0.672

Gnomad ASJ AF: 0.549

Gnomad EAS AF: 0.839

Gnomad SAS AF: 0.533

Gnomad FIN AF: 0.652

Gnomad MID AF: 0.554

Gnomad NFE AF: 0.615

Gnomad OTH AF: 0.532

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

GnomAD4 genome AF: 0.515 AC: 78182 AN: 151912 Hom.: 23100 Cov.: 32 AF XY: 0.522 AC XY: 38755 AN XY: 74250

African (AFR) AF: 0.211 AC: 8730 AN: 41430

American (AMR) AF: 0.672 AC: 10240 AN: 15232

Ashkenazi Jewish (ASJ) AF: 0.549 AC: 1904 AN: 3466

East Asian (EAS) AF: 0.838 AC: 4340 AN: 5176

South Asian (SAS) AF: 0.532 AC: 2567 AN: 4822

European-Finnish (FIN) AF: 0.652 AC: 6877 AN: 10544

Middle Eastern (MID) AF: 0.554 AC: 163 AN: 294

European-Non Finnish (NFE) AF: 0.615 AC: 41775 AN: 67930

Other (OTH) AF: 0.528 AC: 1114 AN: 2108

Alfa AF: 0.585 Hom.: 44034

Bravo AF: 0.504

Asia WGS AF: 0.644 AC: 2241 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.71
CADD	Benign	7.6
DANN	Benign	0.78
PhyloP100		-0.83

Splicing

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

Other links and lift over

dbSNP: rs6768946; hg19: chr3-28993507;