NM_007118.4:c.1854+1316T>C

Variant names:

• chr5-14332216-T-C
• rs30623
• NM_007118.4:c.1854+1316T>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.1854+1316T>C variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.539 in 152,106 control chromosomes in the GnomAD database, including 22,815 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 0.54 (22815 hom., cov: 32)
• Consequence: TRIO NM_007118.4 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 0.583
• Publications: 6 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=-0.83).
• BA1: GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.615 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
TRIO	NM_007118.4	c.1854+1316T>C		intron_variant	Intron 10 of 56	ENST00000344204.9	NP_009049.2

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
TRIO	ENST00000344204.9	c.1854+1316T>C		intron_variant	Intron 10 of 56	1	NM_007118.4	ENSP00000339299.4

Frequencies

GnomAD3 genomes AF: 0.539 AC: 81925 AN: 151988 Hom.: 22812 Cov.: 32

Gnomad AFR AF: 0.405

Gnomad AMI AF: 0.554

Gnomad AMR AF: 0.490

Gnomad ASJ AF: 0.509

Gnomad EAS AF: 0.634

Gnomad SAS AF: 0.448

Gnomad FIN AF: 0.728

Gnomad MID AF: 0.538

Gnomad NFE AF: 0.603

Gnomad OTH AF: 0.543

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

GnomAD4 genome AF: 0.539 AC: 81956 AN: 152106 Hom.: 22815 Cov.: 32 AF XY: 0.541 AC XY: 40251 AN XY: 74356

African (AFR) AF: 0.404 AC: 16775 AN: 41488

American (AMR) AF: 0.490 AC: 7486 AN: 15278

Ashkenazi Jewish (ASJ) AF: 0.509 AC: 1766 AN: 3470

East Asian (EAS) AF: 0.633 AC: 3282 AN: 5186

South Asian (SAS) AF: 0.449 AC: 2163 AN: 4816

European-Finnish (FIN) AF: 0.728 AC: 7703 AN: 10580

Middle Eastern (MID) AF: 0.534 AC: 157 AN: 294

European-Non Finnish (NFE) AF: 0.603 AC: 40970 AN: 67974

Other (OTH) AF: 0.545 AC: 1150 AN: 2110

Alfa AF: 0.570 Hom.: 76934

Bravo AF: 0.517

Asia WGS AF: 0.491 AC: 1704 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.83
CADD	Benign	7.8
DANN	Benign	0.57
PhyloP100		0.58
Mutation Taster		=100/0	polymorphism (auto)

Splicing

Name	Calibrated prediction	Score	Prediction
SpliceAI score (max)		0.050		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: rs30623; hg19: chr5-14332325;