Variant rs146739260 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_007118.4(TRIO):c.2588-12T>A variant causes a splice polypyrimidine tract, intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00775 in 1,604,768 control chromosomes in the GnomAD database, including 92 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Likely benign (★★).

Frequency

Genomes: 𝑓 0.0055 ( 8 hom., cov: 33)

Exomes 𝑓: 0.0080 ( 84 hom. )

Consequence

TRIO
NM_007118.4 splice_polypyrimidine_tract, intron

Scores

Splicing: ADA: 0.07208

Clinical Significance

Benign/Likely benign criteria provided, multiple submitters, no conflicts B:2

Conservation

PhyloP100: -0.878

Variant links:

Genes affected

TRIO (HGNC:12303): (trio Rho guanine nucleotide exchange factor) This gene encodes a large protein that functions as a GDP to GTP exchange factor. This protein promotes the reorganization of the actin cytoskeleton, thereby playing a role in cell migration and growth. Alternative splicing results in multiple transcript variants. [provided by RefSeq, Dec 2015]

TRIO 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=-0.77).

BP6

Variant 5-14364638-T-A is Benign according to our data. Variant chr5-14364638-T-A is described in ClinVar as [Likely_benign]. Clinvar id is 445482.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars.

BS1

Variant frequency is greater than expected in population sas. gnomad4 allele frequency = 0.0055 (837/152312) while in subpopulation SAS AF= 0.00995 (48/4826). AF 95% confidence interval is 0.00771. There are 8 homozygotes in gnomad4. There are 411 alleles in male gnomad4 subpopulation. Median coverage is 33. This position pass quality control queck.

BS2

High AC in GnomAd4 at 837 AD gene.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
TRIO	NM_007118.4 linkuse as main transcript	c.2588-12T>A		splice_polypyrimidine_tract_variant, intron_variant		ENST00000344204.9

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
TRIO	ENST00000344204.9 linkuse as main transcript	c.2588-12T>A		splice_polypyrimidine_tract_variant, intron_variant		1	NM_007118.4	P1	O75962-1

Frequencies

GnomAD3 genomes

AF:

0.00552

AC:

840

AN:

152194

Hom.:

Cov.:

show subpopulations

Gnomad AFR

AF:

0.00157

Gnomad AMI

AF:

0.0252

Gnomad AMR

AF:

0.00380

Gnomad ASJ

AF:

0.0280

Gnomad EAS

AF:

0.00

Gnomad SAS

AF:

0.0104

Gnomad FIN

AF:

0.00518

Gnomad MID

AF:

0.00949

Gnomad NFE

AF:

0.00698

Gnomad OTH

AF:

0.00669

GnomAD3 exomes

AF:

0.00728

AC:

1776

AN:

243946

Hom.:

AF XY:

0.00817

AC XY:

1078

AN XY:

131932

show subpopulations

Gnomad AFR exome

AF:

0.00106

Gnomad AMR exome

AF:

0.00188

Gnomad ASJ exome

AF:

0.0241

Gnomad EAS exome

AF:

0.0000555

Gnomad SAS exome

AF:

0.0168

Gnomad FIN exome

AF:

0.00537

Gnomad NFE exome

AF:

0.00731

Gnomad OTH exome

AF:

0.00848

GnomAD4 exome

AF:

0.00798

AC:

11595

AN:

1452456

Hom.:

Cov.:

AF XY:

0.00822

AC XY:

5936

AN XY:

721976

show subpopulations

Gnomad4 AFR exome

AF:

0.00112

Gnomad4 AMR exome

AF:

0.00250

Gnomad4 ASJ exome

AF:

0.0249

Gnomad4 EAS exome

AF:

0.0000760

Gnomad4 SAS exome

AF:

0.0164

Gnomad4 FIN exome

AF:

0.00452

Gnomad4 NFE exome

AF:

0.00767

Gnomad4 OTH exome

AF:

0.00876

GnomAD4 genome

AF:

0.00550

AC:

837

AN:

152312

Hom.:

Cov.:

AF XY:

0.00552

AC XY:

411

AN XY:

74496

show subpopulations

Gnomad4 AFR

AF:

0.00156

Gnomad4 AMR

AF:

0.00379

Gnomad4 ASJ

AF:

0.0280

Gnomad4 EAS

AF:

0.00

Gnomad4 SAS

AF:

0.00995

Gnomad4 FIN

AF:

0.00518

Gnomad4 NFE

AF:

0.00698

Gnomad4 OTH

AF:

0.00662

Alfa

AF:

0.00818

Hom.:

Bravo

AF:

0.00535

Asia WGS

AF:

0.00491

AC:

AN:

3478

ClinVar

Significance: Benign/Likely benign

Submissions summary: Benign:2

Revision: criteria provided, multiple submitters, no conflicts

LINK: link

Submissions by phenotype

not provided

Benign:2

Benign, criteria provided, single submitter	clinical testing	GeneDx	Aug 27, 2019	- -
Likely benign, criteria provided, single submitter	clinical testing	Center for Pediatric Genomic Medicine, Children's Mercy Hospital and Clinics	Jun 29, 2017	- -

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

BayesDel_noAF

Benign

-0.77

CADD

Benign

7.5

DANN

Benign

0.78

Splicing

Name

Calibrated prediction

Score

Prediction

dbscSNV1_ADA

Benign

0.072

dbscSNV1_RF

Benign

0.25

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

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