ENST00000635992.1:n.*408+127620T>G

Variant names:

• chr3-28992912-T-G
• rs2167089
• ENST00000635992.1:n.*408+127620T>G

Variant summary

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

The ENST00000635992.1(ENSG00000283563):​n.*408+127620T>G variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.722 in 152,126 control chromosomes in the GnomAD database, including 39,771 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 0.72 (39771 hom., cov: 33)
• Consequence: ENSG00000283563 ENST00000635992.1 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.145
• Publications: 6 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=-0.89).
• BA1: GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.916 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+127620T>G		intron_variant	Intron 7 of 13	5		ENSP00000489994.1

Frequencies

GnomAD3 genomes AF: 0.722 AC: 109711 AN: 152008 Hom.: 39747 Cov.: 33

Gnomad AFR AF: 0.682

Gnomad AMI AF: 0.689

Gnomad AMR AF: 0.788

Gnomad ASJ AF: 0.726

Gnomad EAS AF: 0.938

Gnomad SAS AF: 0.623

Gnomad FIN AF: 0.735

Gnomad MID AF: 0.729

Gnomad NFE AF: 0.720

Gnomad OTH AF: 0.722

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

GnomAD4 genome AF: 0.722 AC: 109787 AN: 152126 Hom.: 39771 Cov.: 33 AF XY: 0.722 AC XY: 53678 AN XY: 74350

African (AFR) AF: 0.682 AC: 28293 AN: 41478

American (AMR) AF: 0.788 AC: 12045 AN: 15286

Ashkenazi Jewish (ASJ) AF: 0.726 AC: 2518 AN: 3470

East Asian (EAS) AF: 0.938 AC: 4859 AN: 5180

South Asian (SAS) AF: 0.623 AC: 3005 AN: 4822

European-Finnish (FIN) AF: 0.735 AC: 7775 AN: 10578

Middle Eastern (MID) AF: 0.718 AC: 211 AN: 294

European-Non Finnish (NFE) AF: 0.720 AC: 48924 AN: 67990

Other (OTH) AF: 0.723 AC: 1529 AN: 2116

Alfa AF: 0.724 Hom.: 35837

Bravo AF: 0.726

Asia WGS AF: 0.768 AC: 2669 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	8.2
DANN	Benign	0.82
PhyloP100		-0.14

Splicing

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

Other links and lift over

dbSNP: rs2167089; hg19: chr3-29034403;