rs358753

Variant names:

• chr5-14426502-C-A
• rs358753
• NM_007118.4:c.5203+6481C>A

Your query was ambiguous. Multiple possible variants found:

• chr5-14426502-C-A
• chr5-14426502-C-G
• chr5-14426502-C-T

Variant summary

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

The NM_007118.4(TRIO):​c.5203+6481C>A variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.496 in 152,116 control chromosomes in the GnomAD database, including 22,116 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 0.50 (22116 hom., cov: 33)
• Consequence: TRIO NM_007118.4 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.0750
• Publications: 3 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=-0.85).
• BA1: GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.881 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
TRIO	NM_007118.4	c.5203+6481C>A		intron_variant	Intron 34 of 56	ENST00000344204.9	NP_009049.2

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
TRIO	ENST00000344204.9	c.5203+6481C>A		intron_variant	Intron 34 of 56	1	NM_007118.4	ENSP00000339299.4

Frequencies

GnomAD3 genomes AF: 0.497 AC: 75520 AN: 151998 Hom.: 22125 Cov.: 33

Gnomad AFR AF: 0.180

Gnomad AMI AF: 0.573

Gnomad AMR AF: 0.521

Gnomad ASJ AF: 0.453

Gnomad EAS AF: 0.903

Gnomad SAS AF: 0.614

Gnomad FIN AF: 0.708

Gnomad MID AF: 0.456

Gnomad NFE AF: 0.613

Gnomad OTH AF: 0.521

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

GnomAD4 genome AF: 0.496 AC: 75521 AN: 152116 Hom.: 22116 Cov.: 33 AF XY: 0.504 AC XY: 37510 AN XY: 74372

African (AFR) AF: 0.180 AC: 7460 AN: 41500

American (AMR) AF: 0.522 AC: 7970 AN: 15282

Ashkenazi Jewish (ASJ) AF: 0.453 AC: 1573 AN: 3472

East Asian (EAS) AF: 0.902 AC: 4673 AN: 5178

South Asian (SAS) AF: 0.615 AC: 2965 AN: 4818

European-Finnish (FIN) AF: 0.708 AC: 7485 AN: 10570

Middle Eastern (MID) AF: 0.463 AC: 136 AN: 294

European-Non Finnish (NFE) AF: 0.613 AC: 41645 AN: 67980

Other (OTH) AF: 0.518 AC: 1093 AN: 2112

Alfa AF: 0.578 Hom.: 21283

Bravo AF: 0.474

Asia WGS AF: 0.687 AC: 2387 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.85
CADD	Benign	3.0
DANN	Benign	0.76
PhyloP100		-0.075
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: rs358753; hg19: chr5-14426611;