ENST00000635992.1:n.*408+22077T>G

Variant names:

• chr3-28887369-T-G
• rs2221154
• ENST00000635992.1:n.*408+22077T>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+22077T>G variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.589 in 152,078 control chromosomes in the GnomAD database, including 28,178 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 0.59 (28178 hom., cov: 32)
• Consequence: ENSG00000283563 ENST00000635992.1 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -1.27
• Publications: 8 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=-1.0).
• BA1: GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.819 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+22077T>G		intron_variant	Intron 7 of 13	5		ENSP00000489994.1

Frequencies

GnomAD3 genomes AF: 0.589 AC: 89493 AN: 151960 Hom.: 28112 Cov.: 32

Gnomad AFR AF: 0.825

Gnomad AMI AF: 0.573

Gnomad AMR AF: 0.538

Gnomad ASJ AF: 0.591

Gnomad EAS AF: 0.437

Gnomad SAS AF: 0.483

Gnomad FIN AF: 0.476

Gnomad MID AF: 0.592

Gnomad NFE AF: 0.493

Gnomad OTH AF: 0.583

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

GnomAD4 genome AF: 0.589 AC: 89624 AN: 152078 Hom.: 28178 Cov.: 32 AF XY: 0.584 AC XY: 43427 AN XY: 74348

African (AFR) AF: 0.826 AC: 34269 AN: 41494

American (AMR) AF: 0.538 AC: 8211 AN: 15272

Ashkenazi Jewish (ASJ) AF: 0.591 AC: 2050 AN: 3470

East Asian (EAS) AF: 0.438 AC: 2266 AN: 5174

South Asian (SAS) AF: 0.483 AC: 2330 AN: 4820

European-Finnish (FIN) AF: 0.476 AC: 5036 AN: 10590

Middle Eastern (MID) AF: 0.599 AC: 175 AN: 292

European-Non Finnish (NFE) AF: 0.493 AC: 33528 AN: 67946

Other (OTH) AF: 0.586 AC: 1236 AN: 2108

Alfa AF: 0.528 Hom.: 63266

Bravo AF: 0.607

Asia WGS AF: 0.510 AC: 1770 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-1.0
CADD	Benign	0.20
DANN	Benign	0.50
PhyloP100		-1.3

Splicing

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

Other links and lift over

dbSNP: rs2221154; hg19: chr3-28928860;