rs56016429

chr22-37754993-A-G

Variant summary

Our verdict is Benign. Variant got -20 ACMG points: 0P and 20B. BP4_Strong BP6_Very_Strong BA1

The NM_001039141.3(TRIOBP):c.5487+9A>G variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0292 in 1,613,678 control chromosomes in the GnomAD database, including 1,019 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★★).

• Frequency:
  • Genomes: 𝑓 0.041 (170 hom., cov: 32)
  • Exomes 𝑓: 0.028 (849 hom.)
• Consequence: TRIOBP NM_001039141.3 intron
• Clinical Significance: Benign criteria provided, multiple submitters, no conflicts B:5
• Conservation: PhyloP100: -1.40

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]

ACMG classification

Verdict is Benign. Variant got -20 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.88).
• BP6: Variant 22-37754993-A-G is Benign according to our data. Variant chr22-37754993-A-G is described in ClinVar as [Benign]. Clinvar id is 43860.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars.
• BA1: GnomAd4 highest subpopulation (SAS) allele frequency at 95% confidence interval = 0.0723 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
TRIOBP	NM_001039141.3	c.5487+9A>G		intron_variant		ENST00000644935.1
TRIOBP	NM_007032.5	c.348+9A>G		intron_variant
TRIOBP	NM_138632.2	c.348+9A>G		intron_variant

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
TRIOBP	ENST00000644935.1	c.5487+9A>G		intron_variant			NM_001039141.3	A2

Frequencies

GnomAD3 genomes AF: 0.0406 AC: 6185 AN: 152182 Hom.: 171 Cov.: 32

Gnomad AFR AF: 0.0746

Gnomad AMI AF: 0.0844

Gnomad AMR AF: 0.0232

Gnomad ASJ AF: 0.0556

Gnomad EAS AF: 0.000962

Gnomad SAS AF: 0.0767

Gnomad FIN AF: 0.0347

Gnomad MID AF: 0.0823

Gnomad NFE AF: 0.0238

Gnomad OTH AF: 0.0411

GnomAD3 exomes AF: 0.0338 AC: 8454 AN: 250168 Hom.: 240 AF XY: 0.0353 AC XY: 4778 AN XY: 135344

Gnomad AFR exome AF: 0.0726

Gnomad AMR exome AF: 0.0174

Gnomad ASJ exome AF: 0.0608

Gnomad EAS exome AF: 0.000218

Gnomad SAS exome AF: 0.0740

Gnomad FIN exome AF: 0.0319

Gnomad NFE exome AF: 0.0258

Gnomad OTH exome AF: 0.0328

GnomAD4 exome AF: 0.0280 AC: 40974 AN: 1461378 Hom.: 849 Cov.: 33 AF XY: 0.0295 AC XY: 21429 AN XY: 726956

Gnomad4 AFR exome AF: 0.0770

Gnomad4 AMR exome AF: 0.0185

Gnomad4 ASJ exome AF: 0.0570

Gnomad4 EAS exome AF: 0.000151

Gnomad4 SAS exome AF: 0.0728

Gnomad4 FIN exome AF: 0.0310

Gnomad4 NFE exome AF: 0.0232

Gnomad4 OTH exome AF: 0.0317

GnomAD4 genome AF: 0.0406 AC: 6188 AN: 152300 Hom.: 170 Cov.: 32 AF XY: 0.0413 AC XY: 3078 AN XY: 74476

Gnomad4 AFR AF: 0.0744

Gnomad4 AMR AF: 0.0231

Gnomad4 ASJ AF: 0.0556

Gnomad4 EAS AF: 0.000964

Gnomad4 SAS AF: 0.0769

Gnomad4 FIN AF: 0.0347

Gnomad4 NFE AF: 0.0238

Gnomad4 OTH AF: 0.0407

Alfa AF: 0.0342 Hom.: 45

Bravo AF: 0.0400

Asia WGS AF: 0.0340 AC: 120 AN: 3478

ClinVar

Significance: Benign

Submissions summary: Benign:5

Revision: criteria provided, multiple submitters, no conflicts

Submissions by phenotype

not specified Benign:3

Benign, criteria provided, single submitter	clinical testing	PreventionGenetics, part of Exact Sciences	-	- -
Benign, criteria provided, single submitter	clinical testing	Laboratory for Molecular Medicine, Mass General Brigham Personalized Medicine	Apr 30, 2012	5487+9A>G in Intron 13 of TRIOBP: This variant is not expected to have clinical significance because it is not located within the conserved splice consensus seq uence and has been identified in 7.2% (269/3738) of African American chromosomes from a broad population by the NHLBI Exome Sequencing Project (http://evs.gs.wa shington.edu/EVS; dbSNP rs56016429). -
Benign, criteria provided, single submitter	clinical testing	GeneDx	Aug 24, 2017	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. -

not provided Benign:2

Benign, criteria provided, single submitter	clinical testing	Invitae	Jan 31, 2024	- -
Benign, criteria provided, single submitter	clinical testing	Athena Diagnostics	Jul 31, 2018	- -

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.88
Cadd	Benign	0.16
Dann	Benign	0.68

Splicing

Name	Calibrated prediction	Score	Prediction
SpliceAI score (max)		0.010		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

Other links and lift over

dbSNP: rs56016429; hg19: chr22-38151000;