rs34506684

Positions:

• chr11-5681496-T-C

Variant summary

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

The NM_033034.3(TRIM5):​c.-61-1258A>G variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.554 in 152,016 control chromosomes in the GnomAD database, including 23,463 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 0.55 (23463 hom., cov: 31)
• Consequence: TRIM5 NM_033034.3 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -1.08

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=-0.82).
• BA1: GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.598 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
TRIM5	NM_033034.3	c.-61-1258A>G		intron_variant		ENST00000380034.8	NP_149023.2

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
TRIM5	ENST00000380034.8	c.-61-1258A>G		intron_variant		2	NM_033034.3	ENSP00000369373	P1

Frequencies

GnomAD3 genomes AF: 0.554 AC: 84130 AN: 151900 Hom.: 23441 Cov.: 31

Gnomad AFR AF: 0.605

Gnomad AMI AF: 0.563

Gnomad AMR AF: 0.541

Gnomad ASJ AF: 0.538

Gnomad EAS AF: 0.473

Gnomad SAS AF: 0.479

Gnomad FIN AF: 0.575

Gnomad MID AF: 0.564

Gnomad NFE AF: 0.535

Gnomad OTH AF: 0.529

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

GnomAD4 genome AF: 0.554 AC: 84207 AN: 152016 Hom.: 23463 Cov.: 31 AF XY: 0.553 AC XY: 41055 AN XY: 74304

Gnomad4 AFR AF: 0.605

Gnomad4 AMR AF: 0.541

Gnomad4 ASJ AF: 0.538

Gnomad4 EAS AF: 0.474

Gnomad4 SAS AF: 0.480

Gnomad4 FIN AF: 0.575

Gnomad4 NFE AF: 0.535

Gnomad4 OTH AF: 0.530

Alfa AF: 0.550 Hom.: 2912

Bravo AF: 0.553

Asia WGS AF: 0.521 AC: 1809 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.82
CADD	Benign	8.2
DANN	Benign	0.52

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: rs34506684; hg19: chr11-5702726;