11-4388667-G-A

Variant names:

• chr11-4388667-G-A
• rs915956
• NM_003141.4:c.505-137C>T

Variant summary

Our verdict is Benign. The variant received -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
• Publications: 6 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=-0.91).
• BA1: GnomAd4 highest subpopulation (SAS) allele frequency at 95% confidence interval = 0.177 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.505-137C>T		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.505-137C>T		intron	N/A	ENSP00000254436.7

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

African (AFR) AF: 0.176 AC: 2870 AN: 16306

American (AMR) AF: 0.147 AC: 4013 AN: 27316

Ashkenazi Jewish (ASJ) AF: 0.235 AC: 3669 AN: 15616

East Asian (EAS) AF: 0.169 AC: 5970 AN: 35256

South Asian (SAS) AF: 0.189 AC: 10466 AN: 55294

European-Finnish (FIN) AF: 0.103 AC: 3560 AN: 34726

Middle Eastern (MID) AF: 0.197 AC: 575 AN: 2918

European-Non Finnish (NFE) AF: 0.143 AC: 55384 AN: 387162

Other (OTH) AF: 0.158 AC: 4998 AN: 31694

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

African (AFR) AF: 0.175 AC: 7220 AN: 41282

American (AMR) AF: 0.148 AC: 2260 AN: 15252

Ashkenazi Jewish (ASJ) AF: 0.238 AC: 825 AN: 3468

East Asian (EAS) AF: 0.164 AC: 844 AN: 5144

South Asian (SAS) AF: 0.187 AC: 899 AN: 4812

European-Finnish (FIN) AF: 0.108 AC: 1146 AN: 10566

Middle Eastern (MID) AF: 0.218 AC: 64 AN: 294

European-Non Finnish (NFE) AF: 0.148 AC: 10069 AN: 67980

Other (OTH) AF: 0.174 AC: 367 AN: 2108

Alfa AF: 0.138 Hom.: 215

Bravo AF: 0.162

Asia WGS AF: 0.180 AC: 625 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.91
CADD	Benign	1.9
DANN	Benign	0.52
PhyloP100		0.086
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: rs915956; hg19: chr11-4409897; COSMIC: COSV54343830; COSMIC: COSV54343830;