rs42404

chr5-14417820-A-G

Variant summary

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

The NM_007118.4(TRIO):c.4960-1958A>G variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.293 in 152,144 control chromosomes in the GnomAD database, including 7,200 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 0.29 (7200 hom., cov: 33)
• Consequence: TRIO NM_007118.4 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -2.90

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 (AMR) allele frequency at 95% confidence interval = 0.353 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
TRIO	NM_007118.4	c.4960-1958A>G		intron_variant		ENST00000344204.9

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
TRIO	ENST00000344204.9	c.4960-1958A>G		intron_variant		1	NM_007118.4	P1

Frequencies

GnomAD3 genomes AF: 0.293 AC: 44567 AN: 152026 Hom.: 7206 Cov.: 33

Gnomad AFR AF: 0.190

Gnomad AMI AF: 0.445

Gnomad AMR AF: 0.361

Gnomad ASJ AF: 0.531

Gnomad EAS AF: 0.107

Gnomad SAS AF: 0.327

Gnomad FIN AF: 0.237

Gnomad MID AF: 0.484

Gnomad NFE AF: 0.346

Gnomad OTH AF: 0.316

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

GnomAD4 genome AF: 0.293 AC: 44581 AN: 152144 Hom.: 7200 Cov.: 33 AF XY: 0.291 AC XY: 21625 AN XY: 74370

Gnomad4 AFR AF: 0.190

Gnomad4 AMR AF: 0.361

Gnomad4 ASJ AF: 0.531

Gnomad4 EAS AF: 0.108

Gnomad4 SAS AF: 0.326

Gnomad4 FIN AF: 0.237

Gnomad4 NFE AF: 0.346

Gnomad4 OTH AF: 0.320

Alfa AF: 0.352 Hom.: 15500

Bravo AF: 0.295

Asia WGS AF: 0.239 AC: 832 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	0.074
Dann	Benign	0.33

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: rs42404; hg19: chr5-14417929;