rs6549878

Positions:

• chr3-28703756-C-A
• chr3-28703756-C-G
• chr3-28703756-C-T

Variant summary

Our verdict is Benign. Variant got -12 ACMG points: 0P and 12B. BP4_Strong BA1

The NR_038840.1(LINC00693):​n.323-53002C>A variant causes a intron, non coding transcript change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.928 in 152,264 control chromosomes in the GnomAD database, including 65,687 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 0.93 (65687 hom., cov: 33)
• Consequence: LINC00693 NR_038840.1 intron, non_coding_transcript
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.670

Genes affected

LINC00693 (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

Verdict is Benign. Variant got -12 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.93).
• BA1: GnomAd4 highest subpopulation (AMR) allele frequency at 95% confidence interval = 0.935 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
LINC00693	NR_038840.1	n.323-53002C>A		intron_variant, non_coding_transcript_variant

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
RBMS3	ENST00000636680.2	c.213+127260C>A		intron_variant		5		ENSP00000490271
RBMS3	ENST00000432518.6	n.810-53002C>A		intron_variant, non_coding_transcript_variant		5
RBMS3	ENST00000443912.5	n.87-32253C>A		intron_variant, non_coding_transcript_variant		4
RBMS3	ENST00000445077.1	n.70-53353C>A		intron_variant, non_coding_transcript_variant		3

Frequencies

GnomAD3 genomes AF: 0.928 AC: 141242 AN: 152146 Hom.: 65637 Cov.: 33

Gnomad AFR AF: 0.916

Gnomad AMI AF: 0.998

Gnomad AMR AF: 0.944

Gnomad ASJ AF: 0.919

Gnomad EAS AF: 0.846

Gnomad SAS AF: 0.824

Gnomad FIN AF: 0.955

Gnomad MID AF: 0.934

Gnomad NFE AF: 0.941

Gnomad OTH AF: 0.929

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

GnomAD4 genome AF: 0.928 AC: 141349 AN: 152264 Hom.: 65687 Cov.: 33 AF XY: 0.926 AC XY: 68922 AN XY: 74456

Gnomad4 AFR AF: 0.916

Gnomad4 AMR AF: 0.944

Gnomad4 ASJ AF: 0.919

Gnomad4 EAS AF: 0.847

Gnomad4 SAS AF: 0.823

Gnomad4 FIN AF: 0.955

Gnomad4 NFE AF: 0.941

Gnomad4 OTH AF: 0.926

Alfa AF: 0.939 Hom.: 80514

Bravo AF: 0.930

Asia WGS AF: 0.824 AC: 2865 AN: 3476

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.93
CADD	Benign	0.35
DANN	Benign	0.33

Splicing

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

Publications

LitVar

Other links and lift over

dbSNP: rs6549878; hg19: chr3-28745247;