11-4391023-T-C

Variant names:

• chr11-4391023-T-C
• rs7947461
• NM_003141.4:c.-49-565A>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.-49-565A>G variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.445 in 151,890 control chromosomes in the GnomAD database, including 15,717 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 0.44 (15717 hom., cov: 33)
• Consequence: TRIM21 NM_003141.4 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 0.308
• 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=-0.93).
• BA1: GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.561 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
TRIM21	NM_003141.4	c.-49-565A>G		intron_variant	Intron 1 of 6	ENST00000254436.8	NP_003132.2

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
TRIM21	ENST00000254436.8	c.-49-565A>G		intron_variant	Intron 1 of 6	1	NM_003141.4	ENSP00000254436.7

Frequencies

GnomAD3 genomes AF: 0.445 AC: 67494 AN: 151772 Hom.: 15710 Cov.: 33

Gnomad AFR AF: 0.315

Gnomad AMI AF: 0.507

Gnomad AMR AF: 0.549

Gnomad ASJ AF: 0.470

Gnomad EAS AF: 0.579

Gnomad SAS AF: 0.333

Gnomad FIN AF: 0.479

Gnomad MID AF: 0.408

Gnomad NFE AF: 0.491

Gnomad OTH AF: 0.442

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

GnomAD4 genome AF: 0.445 AC: 67525 AN: 151890 Hom.: 15717 Cov.: 33 AF XY: 0.443 AC XY: 32903 AN XY: 74220

African (AFR) AF: 0.315 AC: 13050 AN: 41456

American (AMR) AF: 0.549 AC: 8384 AN: 15274

Ashkenazi Jewish (ASJ) AF: 0.470 AC: 1630 AN: 3466

East Asian (EAS) AF: 0.579 AC: 2990 AN: 5168

South Asian (SAS) AF: 0.333 AC: 1609 AN: 4828

European-Finnish (FIN) AF: 0.479 AC: 5044 AN: 10526

Middle Eastern (MID) AF: 0.418 AC: 122 AN: 292

European-Non Finnish (NFE) AF: 0.491 AC: 33297 AN: 67864

Other (OTH) AF: 0.445 AC: 939 AN: 2108

Alfa AF: 0.315 Hom.: 821

Bravo AF: 0.450

Asia WGS AF: 0.452 AC: 1571 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.93
CADD	Benign	4.3
DANN	Benign	0.72
PhyloP100		0.31
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: rs7947461; hg19: chr11-4412253;