3-28678635-C-T

Position:

• chr3-28678635-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.323-78123C>T 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 0.102 in 152,172 control chromosomes in the GnomAD database, including 1,050 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 0.10 (1050 hom., cov: 32)
• Consequence: LINC00693 NR_038840.1 intron, non_coding_transcript
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 0.00200

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=-0.89).
• BA1: GnomAd4 highest subpopulation (SAS) allele frequency at 95% confidence interval = 0.174 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
LINC00693	NR_038840.1	n.323-78123C>T		intron_variant, non_coding_transcript_variant

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
RBMS3	ENST00000636680.2	c.213+102139C>T		intron_variant		5
RBMS3	ENST00000432518.6	n.810-78123C>T		intron_variant, non_coding_transcript_variant		5
RBMS3	ENST00000443912.5	n.87-57374C>T		intron_variant, non_coding_transcript_variant		4
RBMS3	ENST00000445077.1	n.70-78474C>T		intron_variant, non_coding_transcript_variant		3

Frequencies

GnomAD3 genomes AF: 0.102 AC: 15506 AN: 152054 Hom.: 1051 Cov.: 32

Gnomad AFR AF: 0.0238

Gnomad AMI AF: 0.128

Gnomad AMR AF: 0.0834

Gnomad ASJ AF: 0.188

Gnomad EAS AF: 0.0886

Gnomad SAS AF: 0.185

Gnomad FIN AF: 0.137

Gnomad MID AF: 0.171

Gnomad NFE AF: 0.138

Gnomad OTH AF: 0.115

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

GnomAD4 genome AF: 0.102 AC: 15496 AN: 152172 Hom.: 1050 Cov.: 32 AF XY: 0.102 AC XY: 7599 AN XY: 74392

Gnomad4 AFR AF: 0.0237

Gnomad4 AMR AF: 0.0833

Gnomad4 ASJ AF: 0.188

Gnomad4 EAS AF: 0.0886

Gnomad4 SAS AF: 0.184

Gnomad4 FIN AF: 0.137

Gnomad4 NFE AF: 0.138

Gnomad4 OTH AF: 0.114

Alfa AF: 0.129 Hom.: 2965

Bravo AF: 0.0936

Asia WGS AF: 0.107 AC: 372 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	3.3
DANN	Benign	0.79

Splicing

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

Publications

LitVar

Other links and lift over

dbSNP: rs17651822; hg19: chr3-28720126;