rs5030768

Positions:

• chr11-4390589-T-C
• chr11-4390589-T-G

Variant summary

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

The NM_003141.4(TRIM21):​c.-49-131A>G variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.154 in 630,200 control chromosomes in the GnomAD database, including 8,557 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 0.16 (2014 hom., cov: 32)
  • Exomes 𝑓: 0.15 (6543 hom.)
• Consequence: TRIM21 NM_003141.4 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.136

Genes affected

TRIM21 (HGNC:11312): (tripartite motif containing 21) This gene encodes a member of the tripartite motif (TRIM) family. The TRIM motif includes three zinc-binding domains, a RING, a B-box type 1 and a B-box type 2, and a coiled-coil region. The encoded protein is part of the RoSSA ribonucleoprotein, which includes a single polypeptide and one of four small RNA molecules. The RoSSA particle localizes to both the cytoplasm and the nucleus. RoSSA interacts with autoantigens in patients with Sjogren syndrome and systemic lupus erythematosus. Alternatively spliced transcript variants for this gene have been described but the full-length nature of only one has been determined. [provided by RefSeq, Jul 2008]

ACMG classification

Verdict is Benign. Variant got -12 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.8).
• BA1: GnomAd4 highest subpopulation (SAS) allele frequency at 95% confidence interval = 0.281 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
TRIM21	NM_003141.4	c.-49-131A>G		intron_variant		ENST00000254436.8

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
TRIM21	ENST00000254436.8	c.-49-131A>G		intron_variant		1	NM_003141.4	P1

Frequencies

GnomAD3 genomes AF: 0.157 AC: 23830 AN: 151972 Hom.: 2012 Cov.: 32

Gnomad AFR AF: 0.185

Gnomad AMI AF: 0.0724

Gnomad AMR AF: 0.122

Gnomad ASJ AF: 0.125

Gnomad EAS AF: 0.280

Gnomad SAS AF: 0.295

Gnomad FIN AF: 0.116

Gnomad MID AF: 0.133

Gnomad NFE AF: 0.138

Gnomad OTH AF: 0.143

GnomAD4 exome AF: 0.153 AC: 73330 AN: 478110 Hom.: 6543 AF XY: 0.159 AC XY: 38778 AN XY: 244474

Gnomad4 AFR exome AF: 0.187

Gnomad4 AMR exome AF: 0.116

Gnomad4 ASJ exome AF: 0.129

Gnomad4 EAS exome AF: 0.258

Gnomad4 SAS exome AF: 0.294

Gnomad4 FIN exome AF: 0.126

Gnomad4 NFE exome AF: 0.132

Gnomad4 OTH exome AF: 0.153

GnomAD4 genome AF: 0.157 AC: 23868 AN: 152090 Hom.: 2014 Cov.: 32 AF XY: 0.158 AC XY: 11743 AN XY: 74352

Gnomad4 AFR AF: 0.185

Gnomad4 AMR AF: 0.122

Gnomad4 ASJ AF: 0.125

Gnomad4 EAS AF: 0.281

Gnomad4 SAS AF: 0.294

Gnomad4 FIN AF: 0.116

Gnomad4 NFE AF: 0.138

Gnomad4 OTH AF: 0.145

Alfa AF: 0.0843 Hom.: 112

Bravo AF: 0.157

Asia WGS AF: 0.279 AC: 973 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.80
CADD	Benign	7.3
DANN	Benign	0.95

Splicing

Name	Calibrated prediction	Score	Prediction
SpliceAI score (max)		0.0		Details are displayed if max score is > 0.2

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

Publications

LitVar

Other links and lift over

dbSNP: rs5030768; hg19: chr11-4411819;