3-28664273-A-G

Variant names:

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

GermlineCancer (beta)

Variant summary

Our verdict is Likely benign.

-4 Likely Benign

-7

-6

-1

0

+5

+6

+9

+10

BenignB

Likely BenignLB

UncertainVUS

Likely PathogenicLP

PathogenicP

The variant received -4 classification points (ACGS-UK Somatic Oncogenicity v2025). B1_Strong

The NR_038840.1(LINC00693):n.322+87777A>G variant causes a intron change involving the alteration of a non-conserved nucleotide. Note: NR_038840.1 is not a MANE Select or MANE Plus Clinical transcript for LINC00693; the reported annotation may differ from that of the MANE-designated reference transcript for this gene. The variant allele was found at a cumulative frequency of 0.626 (AC=95,218) in the gnomAD database across 152,020 control chromosomes, including 30,314 homozygotes. The grpmax filtering allele frequency (95% CI) is 0.767. In-silico predictor (BayesDel (noAF)) classifies this variant as likely benign. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar.

• Frequency: Genomes: 𝑓 0.63 (30314 hom., cov: 32)
• Consequence: LINC00693 NR_038840.1 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.285
• Publications: 24 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): ()

Classification according to ACGS-UK Somatic Oncogenicity v2025

Classification was made for transcript:

Our verdict: Likely_benign. The variant received -4 points.

Apply	Criterion Code & Title / Strength	Strength	Rationale / Clinical Context
	B1High frequency in general population		GnomAD effective popmax AF >1% — B1 stand-alone benign; GnomAD effective popmax AF = 0.767 — exceeds 1% threshold (B1 applied)

Variant Effect in Transcripts

Automated classification analysis was done for transcript: NR_038840.1. You can select a different transcript below to see updated classification assignments.

RefSeq Transcripts

Sel.	Gene / Transcript	Tags	HGVSc / HGVSp	Effect	Exon rank	Protein / UniProt
	LINC00693 NR_038840.1		n.322+87777A>G	intron	Intron 2 of 4	Prot:

LINC00693 NR_038840.1

HGVSc / HGVSpn.322+87777A>G

Exon rankIntron 2 of 4

intron

Prot:

Ensembl Transcripts

Sel.	Gene / Transcript	Tags	HGVSc / HGVSp	Effect	Exon rank	Protein / UniProt
	ENSG00000283563 ENST00000635992.1	TSL:5	n.*339+87777A>G	intron	Intron 6 of 13	Prot: ENSP00000489994.1 UniProt:
	RBMS3 ENST00000636680.2	TSL:5	c.213+87777A>G	intron	Intron 1 of 16	Prot: ENSP00000490271.2 UniProt:
	RBMS3 ENST00000432518.6	TSL:5	n.809+87777A>G	intron	Intron 2 of 4	Prot:

ENSG00000283563 ENST00000635992.1

TSL:5

HGVSc / HGVSpn.*339+87777A>G

Exon rankIntron 6 of 13

intron

Prot: ENSP00000489994.1UniProt: A0A1B0GU75

RBMS3 ENST00000636680.2

TSL:5

HGVSc / HGVSpc.213+87777A>G

Exon rankIntron 1 of 16

intron

Prot: ENSP00000490271.2UniProt: A0A1B0GUW5

RBMS3 ENST00000432518.6

TSL:5

HGVSc / HGVSpn.809+87777A>G

Exon rankIntron 2 of 4

intron

Prot:

Frequencies

Allele frequencies (AF), counts (AC/AN), homozygotes and coverage

Common (AF > 0.05 / Hom > 5)

Rare (AF ≤ 0.0001 / Hom ≤ 1)

Source / population	AF	AC	Hom	AN	Coverage
Global population databases 4 sources Large-scale international reference populations
GnomAD3 genomes	AF: 0.627	AC:95172	Hom:30306	AN:151902	Cov:32
GnomAD4 genome	AF: 0.626	AC:95218	Hom:30314	AN:152020	Cov:32
TOPMed (Bravo)	AF: 0.631	AC:	Hom:	AN:	Cov:
ALFA (dbGaP/dbSNP Allele Frequency Aggregator)	AF: 0.643	AC:374193	Hom:121691	AN:581790	Cov:
Local & regional cohorts 10 sources Population-specific and national genomic databases
ABraOM SABE-WGS-1171	AF: 0.646	AC:1513	Hom:509	AN:2342	Cov:
ChinaMAP Phase 1	AF: 0.810	AC:	Hom:	AN:	Cov:
Denmark Genome	AF: 0.597	AC:179	Hom:	AN:300	Cov:
GenomeAsia100K	AF: 0.682	AC:2375	Hom:	AN:3478	Cov:
Korea4K (4,157 Koreans)	AF: 0.774	AC:5597	Hom:	AN:7234	Cov:
Qatari Genome	AF: 0.676	AC:119	Hom:	AN:176	Cov:
ToMMo 61KJPN (+60KJPN MNV)	AF: 0.706	AC:86702	Hom:30620	AN:122840	Cov:
Turkish Variome	AF: 0.673	AC:1041	Hom:366	AN:1546	Cov:
UK10K	AF: 0.652	AC:4929	Hom:	AN:7562	Cov:
WBBC (Westlake BioBank for Chinese) pilot	AF: 0.814	AC:7289	Hom:2977	AN:8960	Cov:

Showing 14 sources

ClinVar

Not reported in ClinVar

Computational Scores

Algorithm	Calibrated pred.	Score	Prediction
AlphaGenome AVI	Benign	0.29
BayesDel_noAF	Benign	-0.90
CADD	Benign	0.18
DANN	Benign	0.66
GPN-Star LLR	N/A	0.55
GPN-Star score	N/A	-0.55
PhyloP100	Benign	-0.28

Showing 7 of 7 scores

Splicing Scores

Algorithm	Calibrated pred.	Score	Prediction
Pangolin (max)	Benign	0.0

Showing 1 of 1 scores

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

MaxEntScan Visualizer can be used to analyze the impact of this mutation on the neighboring sequence.

MaveDB functional evidence

MaveDB is a public repository of laboratory assays that test the effect of thousands of variants at once — treat this as supporting research data and interpret it with great caution; it is not a clinical classification.

No MaveDB functional evidence found for this variant.

Other links and lift over

dbSNP: rs7617877;

hg19: chr3-28705764;

ACMG debug oncogenicity

ACGS debug oncogenicity

ACMG debug germline

Submit to ClinVar