22-37701352-C-G

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

2

Clinical Significance

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

Conservation

PhyloP100: -0.170

Publications

11 publications found
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 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

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
TRIOBPNM_001039141.3 linkc.-14C>G 5_prime_UTR_variant Exon 3 of 24 ENST00000644935.1 NP_001034230.1 Q9H2D6-1

Ensembl

Gene Transcript HGVSc HGVSp Effect Exon rank TSL MANE Protein Appris UniProt
ENSG00000100101ENST00000455236.4 linkn.*323C>G non_coding_transcript_exon_variant Exon 9 of 13 5 ENSP00000477208.1 V9GYY5
TRIOBPENST00000644935.1 linkc.-14C>G 5_prime_UTR_variant Exon 3 of 24 NM_001039141.3 ENSP00000496394.1 Q9H2D6-1
ENSG00000100101ENST00000455236.4 linkn.*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.:
32
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.:
29
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
0
12231
24462
36692
48923
61154
0.00
0.20
0.40
0.60
0.80
0.95
Allele balance

Age Distribution

Exome Het
Exome Hom
Variant carriers
0
8362
16724
25086
33448
41810
<30
30-35
35-40
40-45
45-50
50-55
55-60
60-65
65-70
70-75
75-80
>80
Age
GnomAD4 genome
AF:
0.188
AC:
28542
AN:
152106
Hom.:
3219
Cov.:
32
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:
67
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
0
1146
2291
3437
4582
5728
0.00
0.20
0.40
0.60
0.80
0.95
Allele balance

Age Distribution

Genome Het
Genome Hom
Variant carriers
0
320
640
960
1280
1600
<30
30-35
35-40
40-45
45-50
50-55
55-60
60-65
65-70
70-75
75-80
>80
Age
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
DANN
Benign
0.54
PhyloP100
-0.17
Mutation Taster
=300/0
polymorphism (auto)

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

Other links and lift over

dbSNP: rs12484441; hg19: chr22-38097359; COSMIC: COSV60376162; API