rs354286

Variant names:

• chr5-14235297-G-A
• rs354286
• NM_007118.4:c.158-35528G>A

Your query was ambiguous. Multiple possible variants found:

• chr5-14235297-G-A
• chr5-14235297-G-C

Variant summary

Our verdict is Benign. The variant received -12 ACMG points: 0P and 12B. BP4_Strong BA1

The NM_007118.4(TRIO):​c.158-35528G>A variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.319 in 152,012 control chromosomes in the GnomAD database, including 7,905 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 0.32 (7905 hom., cov: 32)
• Consequence: TRIO NM_007118.4 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 0.0290
• Publications: 5 publications found

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 Gene-Disease associations (from GenCC):

• syndromic intellectual disability

  Inheritance: AD Classification: DEFINITIVE Submitted by: ClinGen, Illumina
• intellectual developmental disorder, autosomal dominant 63, with macrocephaly

  Inheritance: AD Classification: STRONG, MODERATE Submitted by: G2P, Ambry Genetics
• micrognathia-recurrent infections-behavioral abnormalities-mild intellectual disability syndrome

  Inheritance: AD Classification: STRONG, SUPPORTIVE Submitted by: Ambry Genetics, Labcorp Genetics (formerly Invitae), Orphanet

ACMG classification

Our verdict: Benign. The variant received -12 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.98).
• BA1: GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.433 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
TRIO	NM_007118.4	c.158-35528G>A		intron_variant	Intron 1 of 56	ENST00000344204.9	NP_009049.2

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
TRIO	ENST00000344204.9	c.158-35528G>A		intron_variant	Intron 1 of 56	1	NM_007118.4	ENSP00000339299.4

Frequencies

GnomAD3 genomes AF: 0.319 AC: 48494 AN: 151894 Hom.: 7892 Cov.: 32

Gnomad AFR AF: 0.334

Gnomad AMI AF: 0.306

Gnomad AMR AF: 0.277

Gnomad ASJ AF: 0.293

Gnomad EAS AF: 0.449

Gnomad SAS AF: 0.393

Gnomad FIN AF: 0.282

Gnomad MID AF: 0.272

Gnomad NFE AF: 0.312

Gnomad OTH AF: 0.309

We have no GnomAD4 exomes data on this position. Probably position not covered by the project.

GnomAD4 genome AF: 0.319 AC: 48542 AN: 152012 Hom.: 7905 Cov.: 32 AF XY: 0.319 AC XY: 23668 AN XY: 74290

African (AFR) AF: 0.335 AC: 13871 AN: 41446

American (AMR) AF: 0.278 AC: 4246 AN: 15288

Ashkenazi Jewish (ASJ) AF: 0.293 AC: 1015 AN: 3466

East Asian (EAS) AF: 0.448 AC: 2318 AN: 5172

South Asian (SAS) AF: 0.392 AC: 1886 AN: 4816

European-Finnish (FIN) AF: 0.282 AC: 2978 AN: 10544

Middle Eastern (MID) AF: 0.269 AC: 79 AN: 294

European-Non Finnish (NFE) AF: 0.312 AC: 21222 AN: 67972

Other (OTH) AF: 0.308 AC: 650 AN: 2110

Alfa AF: 0.310 Hom.: 11453

Bravo AF: 0.317

Asia WGS AF: 0.427 AC: 1483 AN: 3476

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.98
CADD	Benign	1.5
DANN	Benign	0.13
PhyloP100		0.029
Mutation Taster		=100/0	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

Other links and lift over

dbSNP: rs354286; hg19: chr5-14235406;