11-5667718-A-G

Variant summary

Our verdict is Benign. Variant got -14 ACMG points: 0P and 14B. BP4_Strong BP6_Moderate BS1 BS2

The NM_033034.3(TRIM5):c.745-7T>C variant causes a splice region, splice polypyrimidine tract, intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00625 in 1,612,794 control chromosomes in the GnomAD database, including 55 homozygotes. In-silico tool predicts a benign outcome for this variant. 3/3 splice prediction tools predict no significant impact on normal splicing. Variant has been reported in ClinVar as Benign (★).

• Frequency:
  • Genomes: 𝑓 0.0042 (2 hom., cov: 32)
  • Exomes 𝑓: 0.0065 (53 hom.)
• Consequence: TRIM5 NM_033034.3 splice_region, splice_polypyrimidine_tract, intron
• Scores: Splicing: ADA: 0.00005742
• Clinical Significance: Benign criteria provided, single submitter B:1
• Conservation: PhyloP100: 2.99

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]

(HGNC:):

ACMG classification

Verdict is Benign. Variant got -14 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.89).
• BP6: Variant 11-5667718-A-G is Benign according to our data. Variant chr11-5667718-A-G is described in ClinVar as [Benign]. Clinvar id is 770213.Status of the report is criteria_provided_single_submitter, 1 stars.
• BS1: Variant frequency is greater than expected in population eas. gnomad4_exome allele frequency = 0.00646 (9435/1460498) while in subpopulation EAS AF= 0.0164 (648/39584). AF 95% confidence interval is 0.0153. There are 53 homozygotes in gnomad4_exome. There are 4570 alleles in male gnomad4_exome subpopulation. Median coverage is 30. This position pass quality control queck.
• BS2: High Homozygotes in GnomAd at 3 AR gene

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
TRIM5	NM_033034.3	c.745-7T>C		splice_region_variant, splice_polypyrimidine_tract_variant, intron_variant		ENST00000380034.8

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
TRIM5	ENST00000380034.8	c.745-7T>C		splice_region_variant, splice_polypyrimidine_tract_variant, intron_variant		2	NM_033034.3	P1

Frequencies

GnomAD3 genomes AF: 0.00425 AC: 647 AN: 152178 Hom.: 3 Cov.: 32

Gnomad AFR AF: 0.00111

Gnomad AMI AF: 0.00

Gnomad AMR AF: 0.00373

Gnomad ASJ AF: 0.00

Gnomad EAS AF: 0.0175

Gnomad SAS AF: 0.00249

Gnomad FIN AF: 0.00329

Gnomad MID AF: 0.00316

Gnomad NFE AF: 0.00586

Gnomad OTH AF: 0.00287

GnomAD3 exomes AF: 0.00553 AC: 1384 AN: 250208 Hom.: 12 AF XY: 0.00551 AC XY: 746 AN XY: 135334

Gnomad AFR exome AF: 0.000989

Gnomad AMR exome AF: 0.00477

Gnomad ASJ exome AF: 0.000398

Gnomad EAS exome AF: 0.0133

Gnomad SAS exome AF: 0.00197

Gnomad FIN exome AF: 0.00292

Gnomad NFE exome AF: 0.00715

Gnomad OTH exome AF: 0.00425

GnomAD4 exome AF: 0.00646 AC: 9435 AN: 1460498 Hom.: 53 Cov.: 30 AF XY: 0.00629 AC XY: 4570 AN XY: 726632

Gnomad4 AFR exome AF: 0.000868

Gnomad4 AMR exome AF: 0.00510

Gnomad4 ASJ exome AF: 0.000230

Gnomad4 EAS exome AF: 0.0164

Gnomad4 SAS exome AF: 0.00238

Gnomad4 FIN exome AF: 0.00330

Gnomad4 NFE exome AF: 0.00702

Gnomad4 OTH exome AF: 0.00560

GnomAD4 genome AF: 0.00424 AC: 646 AN: 152296 Hom.: 2 Cov.: 32 AF XY: 0.00427 AC XY: 318 AN XY: 74478

Gnomad4 AFR AF: 0.00111

Gnomad4 AMR AF: 0.00373

Gnomad4 ASJ AF: 0.00

Gnomad4 EAS AF: 0.0176

Gnomad4 SAS AF: 0.00229

Gnomad4 FIN AF: 0.00329

Gnomad4 NFE AF: 0.00587

Gnomad4 OTH AF: 0.00284

Alfa AF: 0.00512 Hom.: 1

Bravo AF: 0.00452

Asia WGS AF: 0.00404 AC: 14 AN: 3478

EpiCase AF: 0.00442

EpiControl AF: 0.00570

ClinVar

Significance: Benign

Submissions summary: Benign:1

Revision: criteria provided, single submitter

Submissions by phenotype

not provided Benign:1

Benign, criteria provided, single submitter

clinical testing

Invitae

Jul 16, 2018

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Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.89
Cadd	Benign	9.6
Dann	Benign	0.65

Splicing

Name	Calibrated prediction	Score	Prediction
dbscSNV1_ADA	Benign	0.000057
dbscSNV1_RF	Benign	0.0040
SpliceAI score (max)		0.060		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: rs55868421; hg19: chr11-5688948;