rs11704996

Variant names:

Your query was ambiguous. Multiple possible variants found:

Variant summary

Our verdict is Benign. Variant got -19 ACMG points: 0P and 19B. BP4_ModerateBP6_Very_StrongBP7BA1

The NM_001039141.3(TRIOBP):c.5550G>A(p.Val1850Val) variant causes a synonymous change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.057 in 1,613,060 control chromosomes in the GnomAD database, including 2,810 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★★).

Frequency

Genomes: 𝑓 0.060 ( 298 hom., cov: 32)

Exomes 𝑓: 0.057 ( 2512 hom. )

Consequence

TRIOBP
NM_001039141.3 synonymous

Scores

Clinical Significance

Benign criteria provided, multiple submitters, no conflicts B:5

Conservation

PhyloP100: 0.474

Variant links:

Genes affected

TRIOBP (HGNC:17009): (TRIO and F-actin binding protein) This gene encodes a protein with an N-terminal pleckstrin homology domain and a C-terminal coiled-coil region. The protein interacts with trio, which is involved with neural tissue development and controlling actin cytoskeleton organization, cell motility and cell growth. The protein also associates with F-actin and stabilizes F-actin structures. Mutations in this gene have been associated with a form of autosomal recessive nonsyndromic deafness. Multiple alternatively spliced transcript variants that would encode different isoforms have been found for this gene, however some transcripts may be subject to nonsense-mediated decay (NMD). [provided by RefSeq, Nov 2008]

TRIOBP links:

Genome browser will be placed here

ACMG classification

Classification made for transcript

Verdict is Benign. Variant got -19 ACMG points.

BP4

Computational evidence support a benign effect (BayesDel_noAF=-0.46).

BP6

Variant 22-37755163-G-A is Benign according to our data. Variant chr22-37755163-G-A is described in ClinVar as [Benign]. Clinvar id is 43862.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars.

BP7

Synonymous conserved (PhyloP=0.474 with no splicing effect.

BA1

GnomAd4 highest subpopulation (AMR) allele frequency at 95% confidence interval = 0.0876 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
TRIOBP	NM_001039141.3 link	c.5550G>A	p.Val1850Val	synonymous_variant	Exon 14 of 24	ENST00000644935.1	NP_001034230.1	Q9H2D6-1
TRIOBP	NM_007032.5 link	c.411G>A	p.Val137Val	synonymous_variant	Exon 4 of 14		NP_008963.3	Q9H2D6-7
TRIOBP	NM_138632.2 link	c.411G>A	p.Val137Val	synonymous_variant	Exon 4 of 8		NP_619538.2	Q9H2D6-6

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
TRIOBP	ENST00000644935.1 link	c.5550G>A	p.Val1850Val	synonymous_variant	Exon 14 of 24		NM_001039141.3	ENSP00000496394.1		Q9H2D6-1

Frequencies

GnomAD3 genomes

AF:

0.0598

AC:

9104

AN:

152134

Hom.:

298

Cov.:

show subpopulations

Gnomad AFR

AF:

0.0542

Gnomad AMI

AF:

0.0967

Gnomad AMR

AF:

0.0915

Gnomad ASJ

AF:

0.0403

Gnomad EAS

AF:

0.0424

Gnomad SAS

AF:

0.0393

Gnomad FIN

AF:

0.0572

Gnomad MID

AF:

0.00949

Gnomad NFE

AF:

0.0605

Gnomad OTH

AF:

0.0468

GnomAD3 exomes

AF:

0.0581

AC:

14454

AN:

248862

Hom.:

500

AF XY:

0.0542

AC XY:

7299

AN XY:

134632

show subpopulations

Gnomad AFR exome

AF:

0.0520

Gnomad AMR exome

AF:

0.109

Gnomad ASJ exome

AF:

0.0386

Gnomad EAS exome

AF:

0.0454

Gnomad SAS exome

AF:

0.0329

Gnomad FIN exome

AF:

0.0505

Gnomad NFE exome

AF:

0.0558

Gnomad OTH exome

AF:

0.0534

GnomAD4 exome

AF:

0.0567

AC:

82808

AN:

1460808

Hom.:

2512

Cov.:

AF XY:

0.0553

AC XY:

40199

AN XY:

726604

show subpopulations

Gnomad4 AFR exome

AF:

0.0559

Gnomad4 AMR exome

AF:

0.104

Gnomad4 ASJ exome

AF:

0.0423

Gnomad4 EAS exome

AF:

0.0320

Gnomad4 SAS exome

AF:

0.0337

Gnomad4 FIN exome

AF:

0.0540

Gnomad4 NFE exome

AF:

0.0581

Gnomad4 OTH exome

AF:

0.0568

GnomAD4 genome

AF:

0.0598

AC:

9109

AN:

152252

Hom.:

298

Cov.:

AF XY:

0.0599

AC XY:

4460

AN XY:

74442

show subpopulations

Gnomad4 AFR

AF:

0.0540

Gnomad4 AMR

AF:

0.0915

Gnomad4 ASJ

AF:

0.0403

Gnomad4 EAS

AF:

0.0425

Gnomad4 SAS

AF:

0.0396

Gnomad4 FIN

AF:

0.0572

Gnomad4 NFE

AF:

0.0605

Gnomad4 OTH

AF:

0.0468

Alfa

AF:

0.0561

Hom.:

272

Bravo

AF:

0.0599

Asia WGS

AF:

0.0440

AC:

156

AN:

3478

EpiCase

AF:

0.0554

EpiControl

AF:

0.0488

ClinVar

Significance: Benign

Submissions summary: Benign:5

Revision: criteria provided, multiple submitters, no conflicts

LINK: link

Submissions by phenotype

not specified

Benign:3

Jun 01, 2017

GeneDx

Significance: Benign

Review Status: criteria provided, single submitter

Collection Method: clinical testing

This variant is considered likely benign or benign based on one or more of the following criteria: it is a conservative change, it occurs at a poorly conserved position in the protein, it is predicted to be benign by multiple in silico algorithms, and/or has population frequency not consistent with disease. -

PreventionGenetics, part of Exact Sciences

Significance: Benign

Review Status: criteria provided, single submitter

Collection Method: clinical testing

- -

May 07, 2012

Laboratory for Molecular Medicine, Mass General Brigham Personalized Medicine

Significance: Benign

Review Status: criteria provided, single submitter

Collection Method: clinical testing

Val1850Val in Exon 14 of TRIOBP: This variant is not expected to have clinical significance because it does not alter an amino acid residue, is not located wit hin the splice consensus sequence, and has been identified in 5.6% (392/7020) of European American chromosomes from a broad population by the NHLBI Exome Sequen cing Project (http://evs.gs.washington.edu/EVS; dbSNP rs11704996). -

not provided

Benign:2

Feb 03, 2025

Labcorp Genetics (formerly Invitae), Labcorp

Significance: Benign

Review Status: criteria provided, single submitter

Collection Method: clinical testing

- -

Breakthrough Genomics, Breakthrough Genomics

Significance: Benign

Review Status: criteria provided, single submitter

Collection Method: not provided

- -

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

BayesDel_noAF

Benign

-0.46

CADD

Benign

9.0

DANN

Benign

0.86

RBP_binding_hub_radar

0.0

RBP_regulation_power_radar

1.7

Splicing

Name

Calibrated prediction

Score

Prediction

SpliceAI score (max)

0.11

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