chr7-30594388-T-C

Position:

• chr7-30594388-T-C

Variant summary

Our verdict is Benign. Variant got -14 ACMG points: 0P and 14B. BP4_Strong BP6_Moderate BA1

The ENST00000675051.1(GARS1):​c.22-4408T>C variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.487 in 152,038 control chromosomes in the GnomAD database, including 21,547 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★).

• Frequency: Genomes: 𝑓 0.49 (21547 hom., cov: 32)
• Consequence: GARS1 ENST00000675051.1 intron
• Clinical Significance: Benign criteria provided, single submitter B:1
• Conservation: PhyloP100: -0.251

Genes affected

GARS1 (HGNC:4162): (glycyl-tRNA synthetase 1) This gene encodes glycyl-tRNA synthetase, one of the aminoacyl-tRNA synthetases that charge tRNAs with their cognate amino acids. The encoded enzyme is an (alpha)2 dimer which belongs to the class II family of tRNA synthetases. It has been shown to be a target of autoantibodies in the human autoimmune diseases, polymyositis or dermatomyositis. Two transcript variants encoding different isoforms have been found for this gene. [provided by RefSeq, Oct 2015]

GARS1-DT (HGNC:48951): (GARS1 divergent transcript)

ACMG classification

Verdict is Benign. Variant got -14 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.81).
• BP6: Variant 7-30594388-T-C is Benign according to our data. Variant chr7-30594388-T-C is described in ClinVar as [Benign]. Clinvar id is 683987.Status of the report is criteria_provided_single_submitter, 1 stars.
• BA1: GnomAd4 highest subpopulation (NFE) allele frequency at 95% confidence interval = 0.643 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
GARS1	ENST00000675051.1	c.22-4408T>C		intron_variant
GARS1-DT	ENST00000426529.6	n.33+323A>G		intron_variant, non_coding_transcript_variant		5
GARS1-DT	ENST00000578994.5	n.99+323A>G		intron_variant, non_coding_transcript_variant		4

Frequencies

GnomAD3 genomes AF: 0.487 AC: 74033 AN: 151918 Hom.: 21550 Cov.: 32

Gnomad AFR AF: 0.155

Gnomad AMI AF: 0.605

Gnomad AMR AF: 0.536

Gnomad ASJ AF: 0.682

Gnomad EAS AF: 0.478

Gnomad SAS AF: 0.415

Gnomad FIN AF: 0.642

Gnomad MID AF: 0.560

Gnomad NFE AF: 0.648

Gnomad OTH AF: 0.518

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

GnomAD4 genome AF: 0.487 AC: 74034 AN: 152038 Hom.: 21547 Cov.: 32 AF XY: 0.484 AC XY: 35959 AN XY: 74302

Gnomad4 AFR AF: 0.154

Gnomad4 AMR AF: 0.536

Gnomad4 ASJ AF: 0.682

Gnomad4 EAS AF: 0.477

Gnomad4 SAS AF: 0.416

Gnomad4 FIN AF: 0.642

Gnomad4 NFE AF: 0.648

Gnomad4 OTH AF: 0.515

Alfa AF: 0.580 Hom.: 8344

Bravo AF: 0.465

Asia WGS AF: 0.413 AC: 1437 AN: 3478

ClinVar

Significance: Benign

Submissions summary: Benign:1

Revision: criteria provided, single submitter

Submissions by phenotype

not provided Benign:1

Benign, criteria provided, single submitter

clinical testing

GeneDx

Jun 14, 2018

This variant is considered likely benign or benign based on one or more of the following criteria: it is a conservative change, it occurs at a poorly conserved position in the protein, it is predicted to be benign by multiple in silico algorithms, and/or has population frequency not consistent with disease. -

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.81
CADD	Benign	3.3
DANN	Benign	0.61

Splicing

Find out detailed SpliceAI scores and Pangolin per-transcript scores at spliceailookup.broadinstitute.org

Publications

LitVar

Other links and lift over

dbSNP: rs2270025; hg19: chr7-30634004;