rs146993126

chr5-14381261-A-G

Variant summary

Our verdict is Benign. Variant got -14 ACMG points: 0P and 14B. BP4_Strong BP6_Moderate BS1 BS2

The NM_007118.4(TRIO):c.3570+9A>G variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.000198 in 1,604,284 control chromosomes in the GnomAD database, including 2 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Likely benign (★).

• Frequency:
  • Genomes: 𝑓 0.00029 (0 hom., cov: 32)
  • Exomes 𝑓: 0.00019 (2 hom.)
• Consequence: TRIO NM_007118.4 intron
• Clinical Significance: Likely benign criteria provided, single submitter B:1
• Conservation: PhyloP100: -0.0680

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]

ACMG classification

Verdict is Benign. Variant got -14 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.84).
• BP6: Variant 5-14381261-A-G is Benign according to our data. Variant chr5-14381261-A-G is described in ClinVar as [Likely_benign]. Clinvar id is 445737.Status of the report is criteria_provided_single_submitter, 1 stars.
• BS1: Variant frequency is greater than expected in population eas. gnomad4 allele frequency = 0.000289 (44/152356) while in subpopulation EAS AF= 0.00771 (40/5190). AF 95% confidence interval is 0.00582. There are 0 homozygotes in gnomad4. There are 21 alleles in male gnomad4 subpopulation. This position pass quality control queck.
• BS2: High AC in GnomAd at 44 AD gene.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
TRIO	NM_007118.4	c.3570+9A>G		intron_variant		ENST00000344204.9

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
TRIO	ENST00000344204.9	c.3570+9A>G		intron_variant		1	NM_007118.4	P1

Frequencies

GnomAD3 genomes AF: 0.000289 AC: 44 AN: 152238 Hom.: 0 Cov.: 32

Gnomad AFR AF: 0.00

Gnomad AMI AF: 0.00

Gnomad AMR AF: 0.00

Gnomad ASJ AF: 0.000576

Gnomad EAS AF: 0.00769

Gnomad SAS AF: 0.00

Gnomad FIN AF: 0.00

Gnomad MID AF: 0.00

Gnomad NFE AF: 0.0000294

Gnomad OTH AF: 0.00

GnomAD3 exomes AF: 0.000611 AC: 146 AN: 238884 Hom.: 2 AF XY: 0.000565 AC XY: 73 AN XY: 129186

Gnomad AFR exome AF: 0.00

Gnomad AMR exome AF: 0.00

Gnomad ASJ exome AF: 0.000328

Gnomad EAS exome AF: 0.00784

Gnomad SAS exome AF: 0.0000710

Gnomad FIN exome AF: 0.00

Gnomad NFE exome AF: 0.00000913

Gnomad OTH exome AF: 0.000173

GnomAD4 exome AF: 0.000188 AC: 273 AN: 1451928 Hom.: 2 Cov.: 31 AF XY: 0.000176 AC XY: 127 AN XY: 722258

Gnomad4 AFR exome AF: 0.00

Gnomad4 AMR exome AF: 0.00

Gnomad4 ASJ exome AF: 0.000354

Gnomad4 EAS exome AF: 0.00593

Gnomad4 SAS exome AF: 0.0000712

Gnomad4 FIN exome AF: 0.00

Gnomad4 NFE exome AF: 0.00000721

Gnomad4 OTH exome AF: 0.000250

GnomAD4 genome AF: 0.000289 AC: 44 AN: 152356 Hom.: 0 Cov.: 32 AF XY: 0.000282 AC XY: 21 AN XY: 74504

Gnomad4 AFR AF: 0.00

Gnomad4 AMR AF: 0.00

Gnomad4 ASJ AF: 0.000576

Gnomad4 EAS AF: 0.00771

Gnomad4 SAS AF: 0.00

Gnomad4 FIN AF: 0.00

Gnomad4 NFE AF: 0.0000294

Gnomad4 OTH AF: 0.00

Alfa AF: 0.0000449 Hom.: 0

Bravo AF: 0.000442

Asia WGS AF: 0.00202 AC: 7 AN: 3478

ClinVar

Significance: Likely benign

Submissions summary: Benign:1

Revision: criteria provided, single submitter

Submissions by phenotype

not provided Benign:1

Likely benign, criteria provided, single submitter

clinical testing

Center for Pediatric Genomic Medicine, Children's Mercy Hospital and Clinics

Jun 05, 2017

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Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.84
Cadd	Benign	0.13
Dann	Benign	0.30

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

LitVar

Other links and lift over

dbSNP: rs146993126; hg19: chr5-14381370;