22-37701352-C-G

Variant names:

Variant summary

Our verdict is Benign. The variant received -12 ACMG points: 0P and 12B. BP4_StrongBA1

The ENST00000455236.4(ENSG00000100101):n.*323C>G variant causes a non coding transcript exon change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.225 in 1,601,948 control chromosomes in the GnomAD database, including 42,494 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 0.19 ( 3219 hom., cov: 32)

Exomes 𝑓: 0.23 ( 39275 hom. )

Consequence

ENSG00000100101
ENST00000455236.4 non_coding_transcript_exon

Scores

Clinical Significance

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

Conservation

PhyloP100: -0.170

Publications

11 publications found

Variant links:

Genes affected

ENSG00000100101 (HGNC:):

ENSG00000100101 links:

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 Gene-Disease associations (from GenCC):

autosomal recessive nonsyndromic hearing loss 28
Inheritance: AR Classification: DEFINITIVE, STRONG Submitted by: Laboratory for Molecular Medicine, Labcorp Genetics (formerly Invitae), PanelApp Australia
hearing loss, autosomal recessive
Inheritance: AR Classification: DEFINITIVE, SUPPORTIVE Submitted by: ClinGen, Orphanet

TRIOBP links:

Genome browser will be placed here

ACMG classification

Classification was made for transcript

Our verdict: Benign. The variant received -12 ACMG points.

BP4

Computational evidence support a benign effect (BayesDel_noAF=-0.81).

BA1

GnomAd4 highest subpopulation (SAS) allele frequency at 95% confidence interval = 0.276 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
TRIOBP	NM_001039141.3 link	c.-14C>G		5_prime_UTR_variant	Exon 3 of 24	ENST00000644935.1	NP_001034230.1	Q9H2D6-1

Ensembl

Gene	Transcript	HGVSc	Effect	Exon rank	TSL	MANE	Protein	UniProt
ENSG00000100101	ENST00000455236.4 link	n.*323C>G	non_coding_transcript_exon_variant	Exon 9 of 13	5		ENSP00000477208.1	V9GYY5
TRIOBP	ENST00000644935.1 link	c.-14C>G	5_prime_UTR_variant	Exon 3 of 24		NM_001039141.3	ENSP00000496394.1	Q9H2D6-1
ENSG00000100101	ENST00000455236.4 link	n.*323C>G	3_prime_UTR_variant	Exon 9 of 13	5		ENSP00000477208.1	V9GYY5

Frequencies

GnomAD3 genomes

AF:

0.188

AC:

28536

AN:

151988

Hom.:

3221

Cov.:

show subpopulations

Gnomad AFR

AF:

0.0539

Gnomad AMI

AF:

0.173

Gnomad AMR

AF:

0.205

Gnomad ASJ

AF:

0.316

Gnomad EAS

AF:

0.172

Gnomad SAS

AF:

0.289

Gnomad FIN

AF:

0.299

Gnomad MID

AF:

0.231

Gnomad NFE

AF:

0.235

Gnomad OTH

AF:

0.210

GnomAD2 exomes

AF:

0.232

AC:

55612

AN:

240224

AF XY:

0.239

show subpopulations

Gnomad AFR exome

AF:

0.0499

Gnomad AMR exome

AF:

0.194

Gnomad ASJ exome

AF:

0.309

Gnomad EAS exome

AF:

0.171

Gnomad FIN exome

AF:

0.291

Gnomad NFE exome

AF:

0.238

Gnomad OTH exome

AF:

0.251

GnomAD4 exome

AF:

0.229

AC:

331487

AN:

1449842

Hom.:

39275

Cov.:

AF XY:

0.232

AC XY:

167148

AN XY:

720930

show subpopulations

African (AFR)

AF:

0.0473

AC:

1574

AN:

33304

American (AMR)

AF:

0.197

AC:

8627

AN:

43706

Ashkenazi Jewish (ASJ)

AF:

0.303

AC:

7833

AN:

25852

East Asian (EAS)

AF:

0.204

AC:

8073

AN:

39530

South Asian (SAS)

AF:

0.297

AC:

25192

AN:

84826

European-Finnish (FIN)

AF:

0.283

AC:

15029

AN:

53110

Middle Eastern (MID)

AF:

0.265

AC:

1524

AN:

5750

European-Non Finnish (NFE)

AF:

0.226

AC:

249786

AN:

1103822

Other (OTH)

AF:

0.231

AC:

13849

AN:

59942

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.494

Heterozygous variant carriers

12231

24462

36692

48923

61154

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

GnomAD4 genome

AF:

0.188

AC:

28542

AN:

152106

Hom.:

3219

Cov.:

AF XY:

0.191

AC XY:

14230

AN XY:

74330

show subpopulations

African (AFR)

AF:

0.0539

AC:

2238

AN:

41530

American (AMR)

AF:

0.205

AC:

3137

AN:

15270

Ashkenazi Jewish (ASJ)

AF:

0.316

AC:

1098

AN:

3472

East Asian (EAS)

AF:

0.173

AC:

893

AN:

5162

South Asian (SAS)

AF:

0.289

AC:

1389

AN:

4812

European-Finnish (FIN)

AF:

0.299

AC:

3155

AN:

10558

Middle Eastern (MID)

AF:

0.228

AC:

AN:

294

European-Non Finnish (NFE)

AF:

0.235

AC:

15962

AN:

67982

Other (OTH)

AF:

0.211

AC:

445

AN:

2114

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.501

Heterozygous variant carriers

1146

2291

3437

4582

5728

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Alfa

AF:

0.229

Hom.:

769

Bravo

AF:

0.172

Asia WGS

AF:

0.242

AC:

843

AN:

3478

ClinVar

Significance: Benign

Submissions summary: Benign:5

Revision: criteria provided, multiple submitters, no conflicts

LINK: link

Submissions by phenotype

not specified

Benign:3

PreventionGenetics, part of Exact Sciences

Significance:Benign

Review Status:criteria provided, single submitter

Collection Method:clinical testing

- -

May 09, 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. -

May 07, 2012

Laboratory for Molecular Medicine, Mass General Brigham Personalized Medicine

Significance:Benign

Review Status:criteria provided, single submitter

Collection Method:clinical testing

-14C>G in Exon 03 of TRIOBP: This variant is not expected to have clinical signi ficance because it has been identified in 23.2% (1567/6740) of European American chromosomes from a broad population by the NHLBI Exome Sequencing Project (http ://evs.gs.washi -

Autosomal recessive nonsyndromic hearing loss 28

Benign:1

Sep 10, 2021

Genome-Nilou Lab

Significance:Benign

Review Status:criteria provided, single submitter

Collection Method:clinical testing

- -

not provided

Benign:1

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

-0.81

CADD

Benign

4.2

(source)

DANN

Benign

0.54

PhyloP100

-0.17

Mutation Taster

=300/0

polymorphism (auto)

(source)

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

You must be logged in to view publications. This limit was set because tens of millions (!) of queries from AI bots are generated daily.

22-37701352-C-G

Variant summary

Frequency

Consequence

Scores

Clinical Significance

Conservation

Publications

ACMG classification

Transcripts

RefSeq

Ensembl

Frequencies

Age Distribution

Age Distribution

ClinVar

Submissions by phenotype

Computational scores

Splicing

Publications

Other links and lift over