rs1377512

Variant names:

• chr11-5798387-A-G
• rs1377512
• ENST00000412903.1:c.-61-118149T>C

Variant summary

Our verdict is Benign. The variant received -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
• Publications: 2 publications found

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

Our verdict: Benign. The variant received -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 rank	MANE	Protein	UniProt

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
TRIM5	ENST00000412903.1	c.-61-118149T>C		intron_variant	Intron 2 of 4	1		ENSP00000388031.1
TRIM5	ENST00000380027.5	c.-441+57365T>C		intron_variant	Intron 3 of 10	5		ENSP00000369366.1

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

African (AFR) AF: 0.439 AC: 18185 AN: 41440

American (AMR) AF: 0.303 AC: 4623 AN: 15242

Ashkenazi Jewish (ASJ) AF: 0.304 AC: 1053 AN: 3466

East Asian (EAS) AF: 0.207 AC: 1066 AN: 5162

South Asian (SAS) AF: 0.263 AC: 1267 AN: 4820

European-Finnish (FIN) AF: 0.300 AC: 3163 AN: 10560

Middle Eastern (MID) AF: 0.349 AC: 102 AN: 292

European-Non Finnish (NFE) AF: 0.298 AC: 20198 AN: 67854

Other (OTH) AF: 0.320 AC: 675 AN: 2108

Alfa AF: 0.320 Hom.: 1031

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
PhyloP100		-0.57
Mutation Taster		=100/0	polymorphism (auto)

Splicing

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

Other links and lift over

dbSNP: rs1377512; hg19: chr11-5819617;