rs27761

chr5-14431871-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.5203+11850A>G variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.508 in 152,040 control chromosomes in the GnomAD database, including 21,832 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 0.51 (21832 hom., cov: 32)
• Consequence: TRIO NM_007118.4 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -2.05

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=-0.97).
• BA1: GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.748 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
TRIO	NM_007118.4	c.5203+11850A>G		intron_variant		ENST00000344204.9

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
TRIO	ENST00000344204.9	c.5203+11850A>G		intron_variant		1	NM_007118.4	P1

Frequencies

GnomAD3 genomes AF: 0.508 AC: 77105 AN: 151922 Hom.: 21803 Cov.: 32

Gnomad AFR AF: 0.755

Gnomad AMI AF: 0.453

Gnomad AMR AF: 0.485

Gnomad ASJ AF: 0.554

Gnomad EAS AF: 0.0972

Gnomad SAS AF: 0.389

Gnomad FIN AF: 0.376

Gnomad MID AF: 0.544

Gnomad NFE AF: 0.421

Gnomad OTH AF: 0.484

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

GnomAD4 genome AF: 0.508 AC: 77195 AN: 152040 Hom.: 21832 Cov.: 32 AF XY: 0.502 AC XY: 37319 AN XY: 74320

Gnomad4 AFR AF: 0.755

Gnomad4 AMR AF: 0.485

Gnomad4 ASJ AF: 0.554

Gnomad4 EAS AF: 0.0976

Gnomad4 SAS AF: 0.388

Gnomad4 FIN AF: 0.376

Gnomad4 NFE AF: 0.421

Gnomad4 OTH AF: 0.486

Alfa AF: 0.449 Hom.: 18782

Bravo AF: 0.520

Asia WGS AF: 0.305 AC: 1065 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.97
Cadd	Benign	0.35
Dann	Benign	0.47

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: rs27761; hg19: chr5-14431980;