rs3824949

Positions:

• chr11-5680179-G-C

Variant summary

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

The NM_033034.3(TRIM5):​c.-2C>G variant causes a 5 prime UTR change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.531 in 1,597,482 control chromosomes in the GnomAD database, including 231,342 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 0.43 (16359 hom., cov: 31)
  • Exomes 𝑓: 0.54 (214983 hom.)
• Consequence: TRIM5 NM_033034.3 5_prime_UTR
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.0950

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]

ACMG classification

Verdict is Benign. Variant got -12 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.84).
• BA1: GnomAd4 highest subpopulation (SAS) allele frequency at 95% confidence interval = 0.567 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
TRIM5	NM_033034.3	c.-2C>G		5_prime_UTR_variant	2/8	ENST00000380034.8

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
TRIM5	ENST00000380034.8	c.-2C>G		5_prime_UTR_variant	2/8	2	NM_033034.3	P1

Frequencies

GnomAD3 genomes AF: 0.435 AC: 66051 AN: 151834 Hom.: 16361 Cov.: 31

Gnomad AFR AF: 0.183

Gnomad AMI AF: 0.600

Gnomad AMR AF: 0.451

Gnomad ASJ AF: 0.545

Gnomad EAS AF: 0.440

Gnomad SAS AF: 0.585

Gnomad FIN AF: 0.524

Gnomad MID AF: 0.462

Gnomad NFE AF: 0.551

Gnomad OTH AF: 0.481

GnomAD3 exomes AF: 0.509 AC: 120882 AN: 237290 Hom.: 32078 AF XY: 0.522 AC XY: 66561 AN XY: 127520

Gnomad AFR exome AF: 0.167

Gnomad AMR exome AF: 0.484

Gnomad ASJ exome AF: 0.541

Gnomad EAS exome AF: 0.443

Gnomad SAS exome AF: 0.591

Gnomad FIN exome AF: 0.529

Gnomad NFE exome AF: 0.552

Gnomad OTH exome AF: 0.521

GnomAD4 exome AF: 0.541 AC: 782116 AN: 1445528 Hom.: 214983 Cov.: 52 AF XY: 0.544 AC XY: 390393 AN XY: 717344

Gnomad4 AFR exome AF: 0.168

Gnomad4 AMR exome AF: 0.482

Gnomad4 ASJ exome AF: 0.541

Gnomad4 EAS exome AF: 0.449

Gnomad4 SAS exome AF: 0.591

Gnomad4 FIN exome AF: 0.526

Gnomad4 NFE exome AF: 0.556

Gnomad4 OTH exome AF: 0.515

GnomAD4 genome AF: 0.435 AC: 66065 AN: 151954 Hom.: 16359 Cov.: 31 AF XY: 0.437 AC XY: 32444 AN XY: 74240

Gnomad4 AFR AF: 0.183

Gnomad4 AMR AF: 0.451

Gnomad4 ASJ AF: 0.545

Gnomad4 EAS AF: 0.439

Gnomad4 SAS AF: 0.585

Gnomad4 FIN AF: 0.524

Gnomad4 NFE AF: 0.551

Gnomad4 OTH AF: 0.482

Alfa AF: 0.505 Hom.: 4163

Bravo AF: 0.418

Asia WGS AF: 0.457 AC: 1592 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.84
CADD	Benign	1.4
DANN	Benign	0.45

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: rs3824949; hg19: chr11-5701409; COSMIC: COSV59900187; COSMIC: COSV59900187;