chr5-14393512-C-T

Position:

• chr5-14393512-C-T

Variant summary

Our verdict is Benign. Variant got -12 ACMG points: 0P and 12B. BP4_Strong BA1

The NM_007118.4(TRIO):​c.4219-526C>T variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.259 in 152,124 control chromosomes in the GnomAD database, including 6,217 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 0.26 (6217 hom., cov: 32)
• Consequence: TRIO NM_007118.4 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 0.169

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 -12 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.94).
• BA1: GnomAd4 highest subpopulation (NFE) allele frequency at 95% confidence interval = 0.351 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
TRIO	NM_007118.4	c.4219-526C>T		intron_variant		ENST00000344204.9	NP_009049.2

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
TRIO	ENST00000344204.9	c.4219-526C>T		intron_variant		1	NM_007118.4	ENSP00000339299	P1

Frequencies

GnomAD3 genomes AF: 0.259 AC: 39348 AN: 152006 Hom.: 6224 Cov.: 32

Gnomad AFR AF: 0.0882

Gnomad AMI AF: 0.318

Gnomad AMR AF: 0.203

Gnomad ASJ AF: 0.229

Gnomad EAS AF: 0.281

Gnomad SAS AF: 0.173

Gnomad FIN AF: 0.423

Gnomad MID AF: 0.206

Gnomad NFE AF: 0.355

Gnomad OTH AF: 0.257

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

GnomAD4 genome AF: 0.259 AC: 39338 AN: 152124 Hom.: 6217 Cov.: 32 AF XY: 0.260 AC XY: 19335 AN XY: 74344

Gnomad4 AFR AF: 0.0879

Gnomad4 AMR AF: 0.203

Gnomad4 ASJ AF: 0.229

Gnomad4 EAS AF: 0.280

Gnomad4 SAS AF: 0.174

Gnomad4 FIN AF: 0.423

Gnomad4 NFE AF: 0.355

Gnomad4 OTH AF: 0.256

Alfa AF: 0.323 Hom.: 11649

Bravo AF: 0.237

Asia WGS AF: 0.193 AC: 671 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.94
CADD	Benign	2.3
DANN	Benign	0.24

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: rs10065203; hg19: chr5-14393621;