rs915956

Positions:

• chr11-4388667-G-A
• chr11-4388667-G-C

Variant summary

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

The NM_003141.4(TRIM21):​c.505-137C>T variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.152 in 758,104 control chromosomes in the GnomAD database, including 9,122 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 (1936 hom., cov: 32)
  • Exomes 𝑓: 0.15 (7186 hom.)
• Consequence: TRIM21 NM_003141.4 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 0.0860

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=-0.91).
• BA1: GnomAd4 highest subpopulation (SAS) allele frequency at 95% confidence interval = 0.177 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
TRIM21	NM_003141.4	c.505-137C>T		intron_variant		ENST00000254436.8	NP_003132.2

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
TRIM21	ENST00000254436.8	c.505-137C>T		intron_variant		1	NM_003141.4	ENSP00000254436	P1

Frequencies

GnomAD3 genomes AF: 0.158 AC: 23910 AN: 151698 Hom.: 1937 Cov.: 32

Gnomad AFR AF: 0.175

Gnomad AMI AF: 0.255

Gnomad AMR AF: 0.149

Gnomad ASJ AF: 0.238

Gnomad EAS AF: 0.163

Gnomad SAS AF: 0.187

Gnomad FIN AF: 0.108

Gnomad MID AF: 0.215

Gnomad NFE AF: 0.148

Gnomad OTH AF: 0.171

GnomAD4 exome AF: 0.151 AC: 91505 AN: 606288 Hom.: 7186 AF XY: 0.153 AC XY: 48876 AN XY: 319788

Gnomad4 AFR exome AF: 0.176

Gnomad4 AMR exome AF: 0.147

Gnomad4 ASJ exome AF: 0.235

Gnomad4 EAS exome AF: 0.169

Gnomad4 SAS exome AF: 0.189

Gnomad4 FIN exome AF: 0.103

Gnomad4 NFE exome AF: 0.143

Gnomad4 OTH exome AF: 0.158

GnomAD4 genome AF: 0.158 AC: 23926 AN: 151816 Hom.: 1936 Cov.: 32 AF XY: 0.155 AC XY: 11517 AN XY: 74218

Gnomad4 AFR AF: 0.175

Gnomad4 AMR AF: 0.148

Gnomad4 ASJ AF: 0.238

Gnomad4 EAS AF: 0.164

Gnomad4 SAS AF: 0.187

Gnomad4 FIN AF: 0.108

Gnomad4 NFE AF: 0.148

Gnomad4 OTH AF: 0.174

Alfa AF: 0.137 Hom.: 202

Bravo AF: 0.162

Asia WGS AF: 0.180 AC: 625 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.91
CADD	Benign	1.9
DANN	Benign	0.52

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: rs915956; hg19: chr11-4409897; COSMIC: COSV54343830; COSMIC: COSV54343830;