3-28757966-A-G

Variant names:

• chr3-28757966-A-G
• rs2306080
• ENST00000635992.1:n.*340-107258A>G

Variant summary

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

The ENST00000635992.1(ENSG00000283563):​n.*340-107258A>G variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0632 in 152,260 control chromosomes in the GnomAD database, including 447 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 0.063 (447 hom., cov: 32)
  • Failed GnomAD Quality Control
• Consequence: ENSG00000283563 ENST00000635992.1 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.979
• Publications: 0 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=-0.83).
• BA1: GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.215 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
LINC00693	NR_038840.1	n.1283A>G		non_coding_transcript_exon_variant	Exon 5 of 5

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
ENSG00000283563	ENST00000635992.1	n.*340-107258A>G		intron_variant	Intron 6 of 13	5		ENSP00000489994.1
RBMS3	ENST00000432518.6	n.1770A>G		non_coding_transcript_exon_variant	Exon 5 of 5	5
RBMS3	ENST00000636680.2	c.214-107258A>G		intron_variant	Intron 1 of 16	5		ENSP00000490271.2

Frequencies

GnomAD3 genomes AF: 0.0631 AC: 9604 AN: 152142 Hom.: 445 Cov.: 32

Gnomad AFR AF: 0.0249

Gnomad AMI AF: 0.0461

Gnomad AMR AF: 0.0570

Gnomad ASJ AF: 0.0913

Gnomad EAS AF: 0.226

Gnomad SAS AF: 0.153

Gnomad FIN AF: 0.0569

Gnomad MID AF: 0.0949

Gnomad NFE AF: 0.0684

Gnomad OTH AF: 0.0707

GnomAD4 exome Data not reliable, filtered out with message: AC0 AC: 0 AN: 0 Hom.: 0 Cov.: 0 AC XY: 0 AN XY: 0

African (AFR) AC: 0 AN: 0

American (AMR) AC: 0 AN: 0

Ashkenazi Jewish (ASJ) AC: 0 AN: 0

East Asian (EAS) AC: 0 AN: 0

South Asian (SAS) AC: 0 AN: 0

European-Finnish (FIN) AC: 0 AN: 0

Middle Eastern (MID) AC: 0 AN: 0

European-Non Finnish (NFE) AC: 0 AN: 0

Other (OTH) AC: 0 AN: 0

GnomAD4 genome AF: 0.0632 AC: 9617 AN: 152260 Hom.: 447 Cov.: 32 AF XY: 0.0654 AC XY: 4870 AN XY: 74452

African (AFR) AF: 0.0249 AC: 1036 AN: 41550

American (AMR) AF: 0.0572 AC: 874 AN: 15284

Ashkenazi Jewish (ASJ) AF: 0.0913 AC: 317 AN: 3472

East Asian (EAS) AF: 0.225 AC: 1165 AN: 5170

South Asian (SAS) AF: 0.153 AC: 740 AN: 4830

European-Finnish (FIN) AF: 0.0569 AC: 604 AN: 10616

Middle Eastern (MID) AF: 0.0986 AC: 29 AN: 294

European-Non Finnish (NFE) AF: 0.0684 AC: 4650 AN: 68018

Other (OTH) AF: 0.0757 AC: 160 AN: 2114

Alfa AF: 0.0630 Hom.: 207

Bravo AF: 0.0597

Asia WGS AF: 0.216 AC: 749 AN: 3476

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.83
CADD	Benign	0.16
DANN	Benign	0.52
PhyloP100		-0.98

Splicing

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

Other links and lift over

dbSNP: rs2306080; hg19: chr3-28799457;