rs7124435

chr11-5680589-G-Achr11-5680589-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.-61-351C>T variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.92 in 152,274 control chromosomes in the GnomAD database, including 64,814 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 0.92 (64814 hom., cov: 33)
• Consequence: TRIM5 NM_033034.3 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -2.70

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=-0.91).
• BA1: GnomAd4 highest subpopulation (NFE) allele frequency at 95% confidence interval = 0.966 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
TRIM5	NM_033034.3	c.-61-351C>T		intron_variant		ENST00000380034.8

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
TRIM5	ENST00000380034.8	c.-61-351C>T		intron_variant		2	NM_033034.3	P1

Frequencies

GnomAD3 genomes AF: 0.920 AC: 139994 AN: 152156 Hom.: 64772 Cov.: 33

Gnomad AFR AF: 0.845

Gnomad AMI AF: 0.990

Gnomad AMR AF: 0.882

Gnomad ASJ AF: 0.927

Gnomad EAS AF: 0.789

Gnomad SAS AF: 0.932

Gnomad FIN AF: 0.980

Gnomad MID AF: 0.927

Gnomad NFE AF: 0.973

Gnomad OTH AF: 0.931

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

GnomAD4 genome AF: 0.920 AC: 140096 AN: 152274 Hom.: 64814 Cov.: 33 AF XY: 0.918 AC XY: 68384 AN XY: 74468

Gnomad4 AFR AF: 0.845

Gnomad4 AMR AF: 0.882

Gnomad4 ASJ AF: 0.927

Gnomad4 EAS AF: 0.789

Gnomad4 SAS AF: 0.932

Gnomad4 FIN AF: 0.980

Gnomad4 NFE AF: 0.972

Gnomad4 OTH AF: 0.931

Alfa AF: 0.939 Hom.: 18439

Bravo AF: 0.909

Asia WGS AF: 0.889 AC: 3095 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.91
Cadd	Benign	0.047
Dann	Benign	0.51

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: rs7124435; hg19: chr11-5701819;