3-28986073-T-C

Variant names:

• chr3-28986073-T-C
• rs7640046
• ENST00000635992.1:n.*408+120781T>C

Variant summary

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

The ENST00000635992.1(ENSG00000283563):​n.*408+120781T>C variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.9 in 152,182 control chromosomes in the GnomAD database, including 61,760 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 0.90 (61760 hom., cov: 31)
• Consequence: ENSG00000283563 ENST00000635992.1 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.537
• 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]

ACMG classification

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

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.91).
• BA1: GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.975 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+120781T>C		intron_variant	Intron 7 of 13	5		ENSP00000489994.1

Frequencies

GnomAD3 genomes AF: 0.900 AC: 136874 AN: 152064 Hom.: 61712 Cov.: 31

Gnomad AFR AF: 0.938

Gnomad AMI AF: 0.809

Gnomad AMR AF: 0.921

Gnomad ASJ AF: 0.885

Gnomad EAS AF: 0.997

Gnomad SAS AF: 0.888

Gnomad FIN AF: 0.909

Gnomad MID AF: 0.858

Gnomad NFE AF: 0.867

Gnomad OTH AF: 0.891

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

GnomAD4 genome AF: 0.900 AC: 136981 AN: 152182 Hom.: 61760 Cov.: 31 AF XY: 0.902 AC XY: 67105 AN XY: 74390

African (AFR) AF: 0.938 AC: 38940 AN: 41526

American (AMR) AF: 0.921 AC: 14078 AN: 15290

Ashkenazi Jewish (ASJ) AF: 0.885 AC: 3069 AN: 3466

East Asian (EAS) AF: 0.997 AC: 5164 AN: 5178

South Asian (SAS) AF: 0.888 AC: 4276 AN: 4816

European-Finnish (FIN) AF: 0.909 AC: 9626 AN: 10592

Middle Eastern (MID) AF: 0.854 AC: 251 AN: 294

European-Non Finnish (NFE) AF: 0.867 AC: 58954 AN: 67996

Other (OTH) AF: 0.893 AC: 1885 AN: 2112

Alfa AF: 0.889 Hom.: 5903

Bravo AF: 0.901

Asia WGS AF: 0.945 AC: 3288 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.91
CADD	Benign	2.4
DANN	Benign	0.79
PhyloP100		-0.54

Splicing

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

Other links and lift over

dbSNP: rs7640046; hg19: chr3-29027564;