rs7612518

Variant names:

• chr3-28714628-G-A
• rs7612518
• ENST00000635992.1:n.*339+138132G>A

Variant summary

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

The ENST00000635992.1(ENSG00000283563):​n.*339+138132G>A variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.448 in 151,948 control chromosomes in the GnomAD database, including 15,402 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 0.45 (15402 hom., cov: 31)
• Consequence: ENSG00000283563 ENST00000635992.1 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 1.01
• 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]

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=-0.89).
• BA1: GnomAd4 highest subpopulation (AMR) allele frequency at 95% confidence interval = 0.49 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
LINC00693	NR_038840.1	n.323-42130G>A		intron_variant	Intron 2 of 4

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
ENSG00000283563	ENST00000635992.1	n.*339+138132G>A		intron_variant	Intron 6 of 13	5		ENSP00000489994.1

Frequencies

GnomAD3 genomes AF: 0.448 AC: 68077 AN: 151828 Hom.: 15395 Cov.: 31

Gnomad AFR AF: 0.396

Gnomad AMI AF: 0.490

Gnomad AMR AF: 0.500

Gnomad ASJ AF: 0.463

Gnomad EAS AF: 0.435

Gnomad SAS AF: 0.330

Gnomad FIN AF: 0.483

Gnomad MID AF: 0.494

Gnomad NFE AF: 0.471

Gnomad OTH AF: 0.451

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

GnomAD4 genome AF: 0.448 AC: 68114 AN: 151948 Hom.: 15402 Cov.: 31 AF XY: 0.446 AC XY: 33159 AN XY: 74266

African (AFR) AF: 0.396 AC: 16397 AN: 41422

American (AMR) AF: 0.500 AC: 7631 AN: 15272

Ashkenazi Jewish (ASJ) AF: 0.463 AC: 1607 AN: 3472

East Asian (EAS) AF: 0.436 AC: 2247 AN: 5156

South Asian (SAS) AF: 0.330 AC: 1592 AN: 4818

European-Finnish (FIN) AF: 0.483 AC: 5082 AN: 10524

Middle Eastern (MID) AF: 0.486 AC: 143 AN: 294

European-Non Finnish (NFE) AF: 0.471 AC: 32024 AN: 67968

Other (OTH) AF: 0.447 AC: 946 AN: 2114

Alfa AF: 0.471 Hom.: 2969

Bravo AF: 0.450

Asia WGS AF: 0.395 AC: 1376 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	12
DANN	Benign	0.68
PhyloP100		1.0

Splicing

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

Other links and lift over

dbSNP: rs7612518; hg19: chr3-28756119;