3-28664273-A-G

Variant names:

• chr3-28664273-A-G
• rs7617877
• ENST00000635992.1:n.*339+87777A>G

Variant summary

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

The ENST00000635992.1(ENSG00000283563):​n.*339+87777A>G variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.626 in 152,020 control chromosomes in the GnomAD database, including 30,314 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 0.63 (30314 hom., cov: 32)
• Consequence: ENSG00000283563 ENST00000635992.1 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.285
• Publications: 23 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]

LINC00693 (HGNC:44526): (long intergenic non-protein coding RNA 693)

ACMG classification

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

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.9).
• BA1: GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.767 is higher than 0.05.

Variant Effect in Transcripts

ACMG analysis was done for transcript: ENST00000635992.1. You can select a different transcript below to see updated ACMG assignments.

RefSeq Transcripts

Selected	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	LINC00693	NR_038840.1		n.322+87777A>G		intron	N/A

Ensembl Transcripts

Selected	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	ENSG00000283563	ENST00000635992.1	TSL:5	n.*339+87777A>G		intron	N/A	ENSP00000489994.1
	RBMS3	ENST00000636680.2	TSL:5	c.213+87777A>G		intron	N/A	ENSP00000490271.2
	RBMS3	ENST00000432518.6	TSL:5	n.809+87777A>G		intron	N/A

Frequencies

GnomAD3 genomes AF: 0.627 AC: 95172 AN: 151902 Hom.: 30306 Cov.: 32

Gnomad AFR AF: 0.520

Gnomad AMI AF: 0.694

Gnomad AMR AF: 0.738

Gnomad ASJ AF: 0.656

Gnomad EAS AF: 0.788

Gnomad SAS AF: 0.598

Gnomad FIN AF: 0.647

Gnomad MID AF: 0.696

Gnomad NFE AF: 0.649

Gnomad OTH AF: 0.648

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

GnomAD4 genome AF: 0.626 AC: 95218 AN: 152020 Hom.: 30314 Cov.: 32 AF XY: 0.630 AC XY: 46810 AN XY: 74276

African (AFR) AF: 0.520 AC: 21563 AN: 41442

American (AMR) AF: 0.739 AC: 11279 AN: 15272

Ashkenazi Jewish (ASJ) AF: 0.656 AC: 2277 AN: 3472

East Asian (EAS) AF: 0.787 AC: 4063 AN: 5162

South Asian (SAS) AF: 0.598 AC: 2884 AN: 4822

European-Finnish (FIN) AF: 0.647 AC: 6833 AN: 10562

Middle Eastern (MID) AF: 0.697 AC: 205 AN: 294

European-Non Finnish (NFE) AF: 0.649 AC: 44123 AN: 67972

Other (OTH) AF: 0.644 AC: 1358 AN: 2110

Alfa AF: 0.646 Hom.: 110699

Bravo AF: 0.631

Asia WGS AF: 0.682 AC: 2375 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.90
CADD	Benign	0.18
DANN	Benign	0.66
PhyloP100		-0.28

Splicing

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

Other links and lift over

dbSNP: rs7617877; hg19: chr3-28705764;