rs181741158

Positions:

Variant summary

Our verdict is Benign. Variant got -7 ACMG points: 2P and 9B. PM2BP4_ModerateBP6_ModerateBP7BS1

The ENST00000407319.7(TRIOBP):c.1224G>A(p.Arg408=) variant causes a synonymous change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00018 in 1,486,872 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Likely benign (★).

Frequency

Genomes: 𝑓 0.00011 ( 0 hom., cov: 33)

Exomes 𝑓: 0.00019 ( 0 hom. )

Consequence

TRIOBP
ENST00000407319.7 synonymous

Scores

Clinical Significance

Likely benign criteria provided, single submitter B:1

Conservation

PhyloP100: 2.03

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 -7 ACMG points.

PM2

Very rare variant in population databases, with high coverage;

BP4

Computational evidence support a benign effect (BayesDel_noAF=-0.29).

BP6

Variant 22-37759455-G-A is Benign according to our data. Variant chr22-37759455-G-A is described in ClinVar as [Likely_benign]. Clinvar id is 179866.Status of the report is criteria_provided_single_submitter, 1 stars.

BP7

Synonymous conserved (PhyloP=2.03 with no splicing effect.

BS1

Variant frequency is greater than expected in population sas. gnomad4_exome allele frequency = 0.000187 (250/1334600) while in subpopulation SAS AF= 0.00237 (198/83706). AF 95% confidence interval is 0.00209. There are 0 homozygotes in gnomad4_exome. There are 167 alleles in male gnomad4_exome subpopulation. Median coverage is 21. This position pass quality control queck.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein
TRIOBP	NM_001039141.3 linkuse as main transcript	c.6324+191G>A		intron_variant		ENST00000644935.1	NP_001034230.1
TRIOBP	NM_138632.2 linkuse as main transcript	c.1224G>A	p.Arg408=	synonymous_variant	8/8		NP_619538.2
TRIOBP	NM_007032.5 linkuse as main transcript	c.1185+191G>A		intron_variant			NP_008963.3

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
TRIOBP	ENST00000407319.7 linkuse as main transcript	c.1224G>A	p.Arg408=	synonymous_variant	8/8	1		ENSP00000383913		Q9H2D6-6
TRIOBP	ENST00000644935.1 linkuse as main transcript	c.6324+191G>A		intron_variant			NM_001039141.3	ENSP00000496394	A2	Q9H2D6-1
TRIOBP	ENST00000403663.6 linkuse as main transcript	c.1185+191G>A		intron_variant		1		ENSP00000386026	P2	Q9H2D6-7
TRIOBP	ENST00000344404.10 linkuse as main transcript	c.*5807+191G>A		intron_variant, NMD_transcript_variant		2		ENSP00000340312

Frequencies

GnomAD3 genomes

AF:

0.000112

AC:

AN:

152154

Hom.:

Cov.:

show subpopulations

Gnomad AFR

AF:

0.00

Gnomad AMI

AF:

0.00

Gnomad AMR

AF:

0.00

Gnomad ASJ

AF:

0.00

Gnomad EAS

AF:

0.000770

Gnomad SAS

AF:

0.00269

Gnomad FIN

AF:

0.00

Gnomad MID

AF:

0.00

Gnomad NFE

AF:

0.00

Gnomad OTH

AF:

0.00

GnomAD3 exomes

AF:

0.000310

AC:

AN:

248760

Hom.:

AF XY:

0.000393

AC XY:

AN XY:

134708

show subpopulations

Gnomad AFR exome

AF:

0.00

Gnomad AMR exome

AF:

0.00

Gnomad ASJ exome

AF:

0.00

Gnomad EAS exome

AF:

0.00

Gnomad SAS exome

AF:

0.00252

Gnomad FIN exome

AF:

0.00

Gnomad NFE exome

AF:

0.00

Gnomad OTH exome

AF:

0.00

GnomAD4 exome

AF:

0.000187

AC:

250

AN:

1334600

Hom.:

Cov.:

AF XY:

0.000249

AC XY:

167

AN XY:

670968

show subpopulations

Gnomad4 AFR exome

AF:

0.00

Gnomad4 AMR exome

AF:

0.00

Gnomad4 ASJ exome

AF:

0.00

Gnomad4 EAS exome

AF:

0.00110

Gnomad4 SAS exome

AF:

0.00237

Gnomad4 FIN exome

AF:

0.00

Gnomad4 NFE exome

AF:

0.00000201

Gnomad4 OTH exome

AF:

0.000125

GnomAD4 genome

AF:

0.000112

AC:

AN:

152272

Hom.:

Cov.:

AF XY:

0.000121

AC XY:

AN XY:

74478

show subpopulations

Gnomad4 AFR

AF:

0.00

Gnomad4 AMR

AF:

0.00

Gnomad4 ASJ

AF:

0.00

Gnomad4 EAS

AF:

0.000772

Gnomad4 SAS

AF:

0.00269

Gnomad4 FIN

AF:

0.00

Gnomad4 NFE

AF:

0.00

Gnomad4 OTH

AF:

0.00

Bravo

AF:

0.0000189

Asia WGS

AF:

0.00231

AC:

AN:

3478

EpiCase

AF:

0.0000545

EpiControl

AF:

0.00

ClinVar

Significance: Likely benign

Submissions summary: Benign:1

Revision: criteria provided, single submitter

LINK: link

Submissions by phenotype

not specified

Benign:1

Likely benign, criteria provided, single submitter

clinical testing

Laboratory for Molecular Medicine, Mass General Brigham Personalized Medicine

Aug 13, 2014

Arg408Arg in exon 8 of TRIOBP: This variant is not expected to have clinical sig nificance because it does not alter an amino acid residue, it is not located wit hin the splice consensus sequence, and it has been identified in 1% (2/178) of J apanese chromosomes by the 1000 Genomes Project (dbSNP rs181741158). -

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

BayesDel_noAF

Benign

-0.29

CADD

Benign

DANN

Benign

0.85

Splicing

Name

Calibrated prediction

Score

Prediction

SpliceAI score (max)

0.040

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