rs2291841

Positions:

• chr11-5689666-A-C

Variant summary

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

The ENST00000412903.1(TRIM5):​c.-61-9428T>G variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.1 in 152,284 control chromosomes in the GnomAD database, including 942 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 0.10 (942 hom., cov: 33)
  • Failed GnomAD Quality Control
• Consequence: TRIM5 ENST00000412903.1 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 0.0510

Genes affected

TRIM5 (HGNC:16276): (tripartite motif containing 5) The protein encoded by this gene is 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 protein forms homo-oligomers via the coilel-coil region and localizes to cytoplasmic bodies. It appears to function as a E3 ubiquitin-ligase and ubiqutinates itself to regulate its subcellular localization. It may play a role in retroviral restriction. Multiple alternatively spliced transcript variants encoding different isoforms have been described for this gene. [provided by RefSeq, Dec 2009]

TRIM22 (HGNC:16379): (tripartite motif containing 22) The protein encoded by this gene is 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. This protein localizes to the cytoplasm and its expression is induced by interferon. The protein is involved in innate immunity against different DNA and RNA viruses. [provided by RefSeq, Oct 2021]

ACMG classification

Verdict is Benign. Variant got -12 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.85).
• BA1: GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.286 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
TRIM5	ENST00000412903.1	c.-61-9428T>G		intron_variant		1
TRIM5	ENST00000380027.5	c.-440-4272T>G		intron_variant		5
TRIM22	ENST00000460454.2	n.57A>C		non_coding_transcript_exon_variant	1/6	2

Frequencies

GnomAD3 genomes AF: 0.0999 AC: 15205 AN: 152166 Hom.: 942 Cov.: 33

Gnomad AFR AF: 0.105

Gnomad AMI AF: 0.104

Gnomad AMR AF: 0.127

Gnomad ASJ AF: 0.0761

Gnomad EAS AF: 0.297

Gnomad SAS AF: 0.174

Gnomad FIN AF: 0.107

Gnomad MID AF: 0.108

Gnomad NFE AF: 0.0711

Gnomad OTH AF: 0.0813

GnomAD4 exome Data not reliable, filtered out with message: AC0 AC: 0 AN: 0 Hom.: 0 Cov.: 0 AC XY: 0 AN XY: 0

GnomAD4 genome AF: 0.100 AC: 15222 AN: 152284 Hom.: 942 Cov.: 33 AF XY: 0.105 AC XY: 7841 AN XY: 74458

Gnomad4 AFR AF: 0.105

Gnomad4 AMR AF: 0.127

Gnomad4 ASJ AF: 0.0761

Gnomad4 EAS AF: 0.298

Gnomad4 SAS AF: 0.174

Gnomad4 FIN AF: 0.107

Gnomad4 NFE AF: 0.0711

Gnomad4 OTH AF: 0.0823

Alfa AF: 0.0838 Hom.: 300

Bravo AF: 0.101

Asia WGS AF: 0.246 AC: 853 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.85
CADD	Benign	5.6
DANN	Benign	0.60

Splicing

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

Publications

LitVar

Other links and lift over

dbSNP: rs2291841; hg19: chr11-5710896;