rs1377512

Positions:

• chr11-5798387-A-G

Variant summary

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

The ENST00000412903.1(TRIM5):​c.-61-118149T>C variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.332 in 151,856 control chromosomes in the GnomAD database, including 8,743 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 0.33 (8743 hom., cov: 32)
• Consequence: TRIM5 ENST00000412903.1 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.571

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=-0.99).
• BA1: GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.433 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
TRIM5	ENST00000412903.1	c.-61-118149T>C		intron_variant		1		ENSP00000388031
TRIM5	ENST00000380027.5	c.-441+57365T>C		intron_variant		5		ENSP00000369366

Frequencies

GnomAD3 genomes AF: 0.332 AC: 50431 AN: 151738 Hom.: 8742 Cov.: 32

Gnomad AFR AF: 0.439

Gnomad AMI AF: 0.156

Gnomad AMR AF: 0.303

Gnomad ASJ AF: 0.304

Gnomad EAS AF: 0.206

Gnomad SAS AF: 0.264

Gnomad FIN AF: 0.300

Gnomad MID AF: 0.344

Gnomad NFE AF: 0.298

Gnomad OTH AF: 0.322

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

GnomAD4 genome AF: 0.332 AC: 50474 AN: 151856 Hom.: 8743 Cov.: 32 AF XY: 0.330 AC XY: 24496 AN XY: 74244

Gnomad4 AFR AF: 0.439

Gnomad4 AMR AF: 0.303

Gnomad4 ASJ AF: 0.304

Gnomad4 EAS AF: 0.207

Gnomad4 SAS AF: 0.263

Gnomad4 FIN AF: 0.300

Gnomad4 NFE AF: 0.298

Gnomad4 OTH AF: 0.320

Alfa AF: 0.315 Hom.: 955

Bravo AF: 0.341

Asia WGS AF: 0.247 AC: 857 AN: 3476

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.99
CADD	Benign	0.87
DANN	Benign	0.31

Splicing

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

Publications

LitVar

Other links and lift over

dbSNP: rs1377512; hg19: chr11-5819617;