5-14143705-G-A

Variant summary

Our verdict is Benign. Variant got -14 ACMG points: 0P and 14B. BP4_Strong BP6_Moderate BS1 BS2

The NM_007118.4(TRIO):c.-21G>A variant causes a 5 prime UTR change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00116 in 975,588 control chromosomes in the GnomAD database, including 5 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Likely benign (★).

• Frequency:
  • Genomes: 𝑓 0.0057 (5 hom., cov: 31)
  • Exomes 𝑓: 0.00038 (0 hom.)
• Consequence: TRIO NM_007118.4 5_prime_UTR
• Clinical Significance: Likely benign criteria provided, single submitter B:1
• Conservation: PhyloP100: -1.26

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 -14 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.86).
• BP6: Variant 5-14143705-G-A is Benign according to our data. Variant chr5-14143705-G-A is described in ClinVar as [Likely_benign]. Clinvar id is 1200733.Status of the report is criteria_provided_single_submitter, 1 stars.
• BS1: Variant frequency is greater than expected in population afr. gnomad4 allele frequency = 0.00565 (820/145098) while in subpopulation AFR AF= 0.019 (771/40572). AF 95% confidence interval is 0.0179. There are 5 homozygotes in gnomad4. There are 395 alleles in male gnomad4 subpopulation. Median coverage is 31. This position pass quality control queck.
• BS2: High AC in GnomAd at 820 AD gene.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
TRIO	NM_007118.4	c.-21G>A		5_prime_UTR_variant	1/57	ENST00000344204.9

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
TRIO	ENST00000344204.9	c.-21G>A		5_prime_UTR_variant	1/57	1	NM_007118.4	P1
TRIO	ENST00000698541.1	c.-21G>A		5_prime_UTR_variant	1/37
TRIO	ENST00000502816.1	n.4G>A		non_coding_transcript_exon_variant	1/5	2
TRIO	ENST00000505971.5	n.4G>A		non_coding_transcript_exon_variant	1/4	3

Frequencies

GnomAD3 genomes AF: 0.00565 AC: 820 AN: 145110 Hom.: 6 Cov.: 31

Gnomad AFR AF: 0.0190

Gnomad AMI AF: 0.00

Gnomad AMR AF: 0.00239

Gnomad ASJ AF: 0.00

Gnomad EAS AF: 0.00

Gnomad SAS AF: 0.00

Gnomad FIN AF: 0.00

Gnomad MID AF: 0.00

Gnomad NFE AF: 0.0000459

Gnomad OTH AF: 0.00550

GnomAD4 exome AF: 0.000378 AC: 314 AN: 830490 Hom.: 0 Cov.: 24 AF XY: 0.000313 AC XY: 120 AN XY: 383650

Gnomad4 AFR exome AF: 0.0175

Gnomad4 AMR exome AF: 0.00

Gnomad4 ASJ exome AF: 0.00

Gnomad4 EAS exome AF: 0.00

Gnomad4 SAS exome AF: 0.0000610

Gnomad4 FIN exome AF: 0.00

Gnomad4 NFE exome AF: 0.00000395

Gnomad4 OTH exome AF: 0.00121

GnomAD4 genome AF: 0.00565 AC: 820 AN: 145098 Hom.: 5 Cov.: 31 AF XY: 0.00560 AC XY: 395 AN XY: 70572

Gnomad4 AFR AF: 0.0190

Gnomad4 AMR AF: 0.00238

Gnomad4 ASJ AF: 0.00

Gnomad4 EAS AF: 0.00

Gnomad4 SAS AF: 0.00

Gnomad4 FIN AF: 0.00

Gnomad4 NFE AF: 0.0000459

Gnomad4 OTH AF: 0.00548

Alfa AF: 0.00491 Hom.: 1

ClinVar

Significance: Likely benign

Submissions summary: Benign:1

Revision: criteria provided, single submitter

Submissions by phenotype

not provided Benign:1

Likely benign, criteria provided, single submitter

clinical testing

GeneDx

Oct 02, 2018

- -

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.86
Cadd	Benign	15
Dann	Benign	0.95

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: rs947187151; hg19: chr5-14143814;