5-14423727-T-C

Variant names:

• chr5-14423727-T-C
• rs890937
• NM_007118.4:c.5203+3706T>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.5203+3706T>C variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.722 in 151,932 control chromosomes in the GnomAD database, including 40,402 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 0.72 (40402 hom., cov: 29)
• Consequence: TRIO NM_007118.4 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.616
• Publications: 4 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=-0.92).
• BA1: GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.898 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
TRIO	NM_007118.4	c.5203+3706T>C		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+3706T>C		intron_variant	Intron 34 of 56	1	NM_007118.4	ENSP00000339299.4

Frequencies

GnomAD3 genomes AF: 0.722 AC: 109604 AN: 151814 Hom.: 40359 Cov.: 29

Gnomad AFR AF: 0.839

Gnomad AMI AF: 0.585

Gnomad AMR AF: 0.646

Gnomad ASJ AF: 0.474

Gnomad EAS AF: 0.920

Gnomad SAS AF: 0.679

Gnomad FIN AF: 0.774

Gnomad MID AF: 0.528

Gnomad NFE AF: 0.664

Gnomad OTH AF: 0.698

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

GnomAD4 genome AF: 0.722 AC: 109707 AN: 151932 Hom.: 40402 Cov.: 29 AF XY: 0.725 AC XY: 53801 AN XY: 74244

African (AFR) AF: 0.840 AC: 34799 AN: 41440

American (AMR) AF: 0.645 AC: 9859 AN: 15274

Ashkenazi Jewish (ASJ) AF: 0.474 AC: 1644 AN: 3468

East Asian (EAS) AF: 0.920 AC: 4723 AN: 5134

South Asian (SAS) AF: 0.680 AC: 3274 AN: 4812

European-Finnish (FIN) AF: 0.774 AC: 8167 AN: 10550

Middle Eastern (MID) AF: 0.537 AC: 158 AN: 294

European-Non Finnish (NFE) AF: 0.664 AC: 45094 AN: 67948

Other (OTH) AF: 0.693 AC: 1457 AN: 2102

Alfa AF: 0.656 Hom.: 15711

Bravo AF: 0.721

Asia WGS AF: 0.767 AC: 2666 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.92
CADD	Benign	0.65
DANN	Benign	0.29
PhyloP100		-0.62
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: rs890937; hg19: chr5-14423836;