11-4390589-T-C

Variant names:

• chr11-4390589-T-C
• rs5030768
• NM_003141.4:c.-49-131A>G

Variant summary

Our verdict is Benign. The variant received -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
• Publications: 3 publications found

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

Our verdict: Benign. The variant received -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.

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_003141.4. You can select a different transcript below to see updated ACMG assignments.

RefSeq Transcripts

Selected	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	TRIM21	NM_003141.4	MANE Select	c.-49-131A>G		intron	N/A	NP_003132.2

Ensembl Transcripts

Selected	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	TRIM21	ENST00000254436.8	TSL:1 MANE Select	c.-49-131A>G		intron	N/A	ENSP00000254436.7

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

African (AFR) AF: 0.187 AC: 2504 AN: 13406

American (AMR) AF: 0.116 AC: 1922 AN: 16582

Ashkenazi Jewish (ASJ) AF: 0.129 AC: 1698 AN: 13206

East Asian (EAS) AF: 0.258 AC: 7900 AN: 30586

South Asian (SAS) AF: 0.294 AC: 9758 AN: 33142

European-Finnish (FIN) AF: 0.126 AC: 3382 AN: 26936

Middle Eastern (MID) AF: 0.140 AC: 275 AN: 1970

European-Non Finnish (NFE) AF: 0.132 AC: 41842 AN: 315896

Other (OTH) AF: 0.153 AC: 4049 AN: 26386

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

African (AFR) AF: 0.185 AC: 7680 AN: 41464

American (AMR) AF: 0.122 AC: 1860 AN: 15284

Ashkenazi Jewish (ASJ) AF: 0.125 AC: 433 AN: 3472

East Asian (EAS) AF: 0.281 AC: 1451 AN: 5166

South Asian (SAS) AF: 0.294 AC: 1417 AN: 4822

European-Finnish (FIN) AF: 0.116 AC: 1230 AN: 10580

Middle Eastern (MID) AF: 0.136 AC: 40 AN: 294

European-Non Finnish (NFE) AF: 0.138 AC: 9385 AN: 67988

Other (OTH) AF: 0.145 AC: 306 AN: 2108

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 v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.80
CADD	Benign	7.3
DANN	Benign	0.95
PhyloP100		-0.14
Mutation Taster		=100/0	polymorphism (auto)

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

Other links and lift over

dbSNP: rs5030768; hg19: chr11-4411819;