5-14189047-G-C

Variant names:

• chr5-14189047-G-C
• rs26133
• NM_007118.4:c.157+45165G>C

Variant summary

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

The NM_007118.4(TRIO):​c.157+45165G>C variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.708 in 152,108 control chromosomes in the GnomAD database, including 39,167 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 0.71 (39167 hom., cov: 33)
• Consequence: TRIO NM_007118.4 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.923

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=-0.89).
• BA1: GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.936 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
TRIO	NM_007118.4	c.157+45165G>C		intron_variant	Intron 1 of 56	ENST00000344204.9	NP_009049.2

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
TRIO	ENST00000344204.9	c.157+45165G>C		intron_variant	Intron 1 of 56	1	NM_007118.4	ENSP00000339299.4

Frequencies

GnomAD3 genomes AF: 0.708 AC: 107676 AN: 151990 Hom.: 39151 Cov.: 33

Gnomad AFR AF: 0.536

Gnomad AMI AF: 0.704

Gnomad AMR AF: 0.692

Gnomad ASJ AF: 0.773

Gnomad EAS AF: 0.959

Gnomad SAS AF: 0.768

Gnomad FIN AF: 0.786

Gnomad MID AF: 0.665

Gnomad NFE AF: 0.778

Gnomad OTH AF: 0.712

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

GnomAD4 genome AF: 0.708 AC: 107731 AN: 152108 Hom.: 39167 Cov.: 33 AF XY: 0.711 AC XY: 52903 AN XY: 74358

Gnomad4 AFR AF: 0.536

Gnomad4 AMR AF: 0.692

Gnomad4 ASJ AF: 0.773

Gnomad4 EAS AF: 0.959

Gnomad4 SAS AF: 0.768

Gnomad4 FIN AF: 0.786

Gnomad4 NFE AF: 0.778

Gnomad4 OTH AF: 0.712

Alfa AF: 0.732 Hom.: 5150

Bravo AF: 0.694

Asia WGS AF: 0.826 AC: 2870 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.89
CADD	Benign	0.15
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: rs26133; hg19: chr5-14189156;