Variant 11-5667718-A-G details in Genebe, Genetics Data Aggregator

Variant summary

Our verdict is Benign. Variant got -20 ACMG points: 0P and 20B. BP4_StrongBP6_Very_StrongBS1BS2

The NM_033034.3(TRIM5):c.745-7T>C variant causes a splice region, 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, intron

Scores

Splicing: ADA: 0.00005742

Clinical Significance

Benign criteria provided, multiple submitters, no conflicts B:2

Conservation

PhyloP100: 2.99

Variant links:

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]

TRIM5 links:

ENSG00000239920 (HGNC:):

ENSG00000239920 links:

Genome browser will be placed here

ACMG classification

Classification made for transcript

Verdict is Benign. Variant got -20 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_multiple_submitters_no_conflicts, 2 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 GnomAd4 at 2 AR gene

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
TRIM5	NM_033034.3 link	c.745-7T>C		splice_region_variant, intron_variant	Intron 4 of 7	ENST00000380034.8	NP_149023.2	Q9C035-1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
TRIM5	ENST00000380034.8 link	c.745-7T>C		splice_region_variant, intron_variant	Intron 4 of 7	2	NM_033034.3	ENSP00000369373.3		Q9C035-1
ENSG00000239920	ENST00000380259.7 link	n.231+10486T>C		intron_variant	Intron 1 of 7	5		ENSP00000369609.3		A0A2U3TZJ3

Frequencies

GnomAD3 genomes

AF:

0.00425

AC:

647

AN:

152178

Hom.:

Cov.:

show subpopulations

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.:

AF XY:

0.00551

AC XY:

746

AN XY:

135334

show subpopulations

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.:

Cov.:

AF XY:

0.00629

AC XY:

4570

AN XY:

726632

show subpopulations

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.:

Cov.:

AF XY:

0.00427

AC XY:

318

AN XY:

74478

show subpopulations

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.:

Bravo

AF:

0.00452

Asia WGS

AF:

0.00404

AC:

AN:

3478

EpiCase

AF:

0.00442

EpiControl

AF:

0.00570

ClinVar

Significance: Benign

Submissions summary: Benign:2

Revision: criteria provided, multiple submitters, no conflicts

LINK: link

Submissions by phenotype

not provided

Benign:2

Breakthrough Genomics, Breakthrough Genomics

Significance: Benign

Review Status: criteria provided, single submitter

Collection Method: not provided

- -

Jul 16, 2018

Labcorp Genetics (formerly Invitae), Labcorp

Significance: Benign

Review Status: criteria provided, single submitter

Collection Method: clinical testing

- -

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

Below is the list of publications found by LitVar. It may be empty.

Variant summary

Frequency

Consequence

Scores

Clinical Significance

Conservation

ACMG classification

Transcripts

RefSeq

Ensembl

Frequencies

ClinVar

Submissions by phenotype

Computational scores

Splicing

Publications

LitVar

Other links and lift over