rs28381979

chr11-5679401-G-Achr11-5679401-G-T

Variant summary

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

The NM_033034.3(TRIM5):c.418-232C>T variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0989 in 152,034 control chromosomes in the GnomAD database, including 796 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 0.099 (796 hom., cov: 32)
• Consequence: TRIM5 NM_033034.3 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -1.06

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=-0.83).
• BA1: GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.127 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
TRIM5	NM_033034.3	c.418-232C>T		intron_variant		ENST00000380034.8

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
TRIM5	ENST00000380034.8	c.418-232C>T		intron_variant		2	NM_033034.3	P1

Frequencies

GnomAD3 genomes AF: 0.0987 AC: 15000 AN: 151916 Hom.: 791 Cov.: 32

Gnomad AFR AF: 0.129

Gnomad AMI AF: 0.0758

Gnomad AMR AF: 0.0827

Gnomad ASJ AF: 0.0979

Gnomad EAS AF: 0.000386

Gnomad SAS AF: 0.0168

Gnomad FIN AF: 0.108

Gnomad MID AF: 0.0759

Gnomad NFE AF: 0.0961

Gnomad OTH AF: 0.101

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

GnomAD4 genome AF: 0.0989 AC: 15035 AN: 152034 Hom.: 796 Cov.: 32 AF XY: 0.0969 AC XY: 7204 AN XY: 74324

Gnomad4 AFR AF: 0.130

Gnomad4 AMR AF: 0.0826

Gnomad4 ASJ AF: 0.0979

Gnomad4 EAS AF: 0.000387

Gnomad4 SAS AF: 0.0168

Gnomad4 FIN AF: 0.108

Gnomad4 NFE AF: 0.0961

Gnomad4 OTH AF: 0.0994

Alfa AF: 0.0916 Hom.: 82

Bravo AF: 0.101

Asia WGS AF: 0.0250 AC: 89 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.83
Cadd	Benign	6.2
Dann	Benign	0.56

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: rs28381979; hg19: chr11-5700631;