rs30616

Positions:

• chr5-14267064-G-A
• chr5-14267064-G-C

Variant summary

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

The NM_007118.4(TRIO):​c.158-3761G>A variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.87 in 152,238 control chromosomes in the GnomAD database, including 57,889 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 0.87 (57889 hom., cov: 32)
• Consequence: TRIO NM_007118.4 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.998

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=-0.9).
• BA1: GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.961 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
TRIO	NM_007118.4	c.158-3761G>A		intron_variant		ENST00000344204.9

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
TRIO	ENST00000344204.9	c.158-3761G>A		intron_variant		1	NM_007118.4	P1

Frequencies

GnomAD3 genomes AF: 0.870 AC: 132411 AN: 152120 Hom.: 57850 Cov.: 32

Gnomad AFR AF: 0.918

Gnomad AMI AF: 0.750

Gnomad AMR AF: 0.784

Gnomad ASJ AF: 0.817

Gnomad EAS AF: 0.984

Gnomad SAS AF: 0.822

Gnomad FIN AF: 0.920

Gnomad MID AF: 0.807

Gnomad NFE AF: 0.852

Gnomad OTH AF: 0.872

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

GnomAD4 genome AF: 0.870 AC: 132513 AN: 152238 Hom.: 57889 Cov.: 32 AF XY: 0.870 AC XY: 64757 AN XY: 74452

Gnomad4 AFR AF: 0.918

Gnomad4 AMR AF: 0.784

Gnomad4 ASJ AF: 0.817

Gnomad4 EAS AF: 0.984

Gnomad4 SAS AF: 0.822

Gnomad4 FIN AF: 0.920

Gnomad4 NFE AF: 0.852

Gnomad4 OTH AF: 0.872

Alfa AF: 0.846 Hom.: 36827

Bravo AF: 0.863

Asia WGS AF: 0.884 AC: 3071 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.90
CADD	Benign	0.047
DANN	Benign	0.49

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: rs30616; hg19: chr5-14267173;