rs173948

chr5-14347662-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.2047-10516A>G variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.373 in 152,184 control chromosomes in the GnomAD database, including 12,435 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 0.37 (12435 hom., cov: 34)
• Consequence: TRIO NM_007118.4 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.231

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]

LOC124900943 (HGNC:):

ACMG classification

Verdict is Benign. Variant got -12 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.91).
• BA1: GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.535 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
TRIO	NM_007118.4	c.2047-10516A>G		intron_variant		ENST00000344204.9
LOC124900943	XR_007058698.1	n.1696A>G		non_coding_transcript_exon_variant	2/2

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
TRIO	ENST00000344204.9	c.2047-10516A>G		intron_variant		1	NM_007118.4	P1

Frequencies

GnomAD3 genomes AF: 0.373 AC: 56780 AN: 152066 Hom.: 12448 Cov.: 34

Gnomad AFR AF: 0.139

Gnomad AMI AF: 0.413

Gnomad AMR AF: 0.378

Gnomad ASJ AF: 0.396

Gnomad EAS AF: 0.553

Gnomad SAS AF: 0.328

Gnomad FIN AF: 0.575

Gnomad MID AF: 0.383

Gnomad NFE AF: 0.471

Gnomad OTH AF: 0.399

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

GnomAD4 genome AF: 0.373 AC: 56764 AN: 152184 Hom.: 12435 Cov.: 34 AF XY: 0.378 AC XY: 28137 AN XY: 74390

Gnomad4 AFR AF: 0.139

Gnomad4 AMR AF: 0.377

Gnomad4 ASJ AF: 0.396

Gnomad4 EAS AF: 0.551

Gnomad4 SAS AF: 0.329

Gnomad4 FIN AF: 0.575

Gnomad4 NFE AF: 0.471

Gnomad4 OTH AF: 0.395

Alfa AF: 0.434 Hom.: 7070

Bravo AF: 0.354

Asia WGS AF: 0.373 AC: 1295 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.91
Cadd	Benign	0.090
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: rs173948; hg19: chr5-14347771;