rs6883134

Positions:

• chr5-14415481-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.4960-4297A>G variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.122 in 152,146 control chromosomes in the GnomAD database, including 1,724 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 0.12 (1724 hom., cov: 32)
• Consequence: TRIO NM_007118.4 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.490

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=-0.8).
• BA1: GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.263 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
TRIO	NM_007118.4	c.4960-4297A>G		intron_variant		ENST00000344204.9	NP_009049.2

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
TRIO	ENST00000344204.9	c.4960-4297A>G		intron_variant		1	NM_007118.4	ENSP00000339299	P1

Frequencies

GnomAD3 genomes AF: 0.122 AC: 18533 AN: 152028 Hom.: 1717 Cov.: 32

Gnomad AFR AF: 0.267

Gnomad AMI AF: 0.0143

Gnomad AMR AF: 0.0895

Gnomad ASJ AF: 0.0484

Gnomad EAS AF: 0.000577

Gnomad SAS AF: 0.0888

Gnomad FIN AF: 0.0827

Gnomad MID AF: 0.101

Gnomad NFE AF: 0.0642

Gnomad OTH AF: 0.118

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

GnomAD4 genome AF: 0.122 AC: 18561 AN: 152146 Hom.: 1724 Cov.: 32 AF XY: 0.121 AC XY: 8996 AN XY: 74402

Gnomad4 AFR AF: 0.267

Gnomad4 AMR AF: 0.0892

Gnomad4 ASJ AF: 0.0484

Gnomad4 EAS AF: 0.000578

Gnomad4 SAS AF: 0.0897

Gnomad4 FIN AF: 0.0827

Gnomad4 NFE AF: 0.0642

Gnomad4 OTH AF: 0.116

Alfa AF: 0.0901 Hom.: 202

Bravo AF: 0.127

Asia WGS AF: 0.0510 AC: 179 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.80
CADD	Benign	2.3
DANN	Benign	0.39

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: rs6883134; hg19: chr5-14415590;