chr7-30622469-T-C

Variant names:

• chr7-30622469-T-C
• rs374795892
• NM_002047.4:c.1613+7T>C

Variant summary

Our verdict is Benign. Variant got -10 ACMG points: 0P and 10B. BP4_Strong BP6_Moderate BS2

The NM_002047.4(GARS1):​c.1613+7T>C variant causes a splice region, intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00000684 in 1,461,752 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a benign outcome for this variant. 3/3 splice prediction tools predict no significant impact on normal splicing. Variant has been reported in ClinVar as Likely benign (★).

• Frequency:
  • Genomes: not found (cov: 32)
  • Exomes 𝑓: 0.0000068 (0 hom.)
• Consequence: GARS1 NM_002047.4 splice_region, intron
• Scores: Splicing: ADA: 0.0004422
• Clinical Significance: Likely benign criteria provided, single submitter B:1
• Conservation: PhyloP100: 0.138

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]

ACMG classification

Verdict is Benign. Variant got -10 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.77).
• BP6: Variant 7-30622469-T-C is Benign according to our data. Variant chr7-30622469-T-C is described in ClinVar as [Likely_benign]. Clinvar id is 476752.Status of the report is criteria_provided_single_submitter, 1 stars.
• BS2: High AC in GnomAdExome4 at 10 AD gene.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
GARS1	NM_002047.4	c.1613+7T>C		splice_region_variant, intron_variant	Intron 12 of 16	ENST00000389266.8	NP_002038.2
GARS1	NM_001316772.1	c.1451+7T>C		splice_region_variant, intron_variant	Intron 12 of 16		NP_001303701.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
GARS1	ENST00000389266.8	c.1613+7T>C		splice_region_variant, intron_variant	Intron 12 of 16	1	NM_002047.4	ENSP00000373918.3
GARS1	ENST00000675651.1	c.1613+7T>C		splice_region_variant, intron_variant	Intron 12 of 16			ENSP00000502513.1
GARS1	ENST00000675810.1	c.1511+7T>C		splice_region_variant, intron_variant	Intron 11 of 15			ENSP00000502743.1
GARS1	ENST00000675693.1	c.1445+7T>C		splice_region_variant, intron_variant	Intron 13 of 17			ENSP00000502174.1
GARS1	ENST00000675051.1	c.1412+7T>C		splice_region_variant, intron_variant	Intron 12 of 16			ENSP00000502296.1
GARS1	ENST00000674815.1	c.1244+7T>C		splice_region_variant, intron_variant	Intron 12 of 16			ENSP00000502799.1
GARS1	ENST00000674851.1	c.1244+7T>C		splice_region_variant, intron_variant	Intron 13 of 17			ENSP00000502451.1
GARS1	ENST00000444666.6	n.1613+7T>C		splice_region_variant, intron_variant	Intron 12 of 17	3		ENSP00000415447.2
GARS1	ENST00000674616.1	n.*1327+7T>C		splice_region_variant, intron_variant	Intron 13 of 17			ENSP00000502408.1
GARS1	ENST00000674643.1	n.*713+7T>C		splice_region_variant, intron_variant	Intron 13 of 16			ENSP00000501636.1
GARS1	ENST00000674737.1	n.*951+7T>C		splice_region_variant, intron_variant	Intron 13 of 17			ENSP00000502464.1
GARS1	ENST00000674807.1	n.1613+7T>C		splice_region_variant, intron_variant	Intron 12 of 15			ENSP00000502814.1
GARS1	ENST00000675529.1	n.*1483+7T>C		splice_region_variant, intron_variant	Intron 13 of 17			ENSP00000501655.1
GARS1	ENST00000675859.1	n.1613+7T>C		splice_region_variant, intron_variant	Intron 12 of 14			ENSP00000502033.1
GARS1	ENST00000676088.1	n.*1555+7T>C		splice_region_variant, intron_variant	Intron 14 of 18			ENSP00000501884.1
GARS1	ENST00000676140.1	n.*558+7T>C		splice_region_variant, intron_variant	Intron 12 of 16			ENSP00000502571.1
GARS1	ENST00000676164.1	n.*1064+7T>C		splice_region_variant, intron_variant	Intron 12 of 16			ENSP00000501986.1
GARS1	ENST00000676210.1	n.*902+7T>C		splice_region_variant, intron_variant	Intron 13 of 17			ENSP00000502373.1
GARS1	ENST00000676259.1	n.*1045+7T>C		splice_region_variant, intron_variant	Intron 12 of 16			ENSP00000501980.1
GARS1	ENST00000676403.1	n.1613+7T>C		splice_region_variant, intron_variant	Intron 12 of 15			ENSP00000502681.1

Frequencies

GnomAD3 genomes Cov.: 32

GnomAD3 exomes AF: 0.0000120 AC: 3 AN: 249504 Hom.: 0 AF XY: 0.0000222 AC XY: 3 AN XY: 135376

Gnomad AFR exome AF: 0.00

Gnomad AMR exome AF: 0.00

Gnomad ASJ exome AF: 0.00

Gnomad EAS exome AF: 0.00

Gnomad SAS exome AF: 0.0000327

Gnomad FIN exome AF: 0.00

Gnomad NFE exome AF: 0.0000177

Gnomad OTH exome AF: 0.00

GnomAD4 exome AF: 0.00000684 AC: 10 AN: 1461752 Hom.: 0 Cov.: 31 AF XY: 0.00000825 AC XY: 6 AN XY: 727194

Gnomad4 AFR exome AF: 0.00

Gnomad4 AMR exome AF: 0.00

Gnomad4 ASJ exome AF: 0.00

Gnomad4 EAS exome AF: 0.00

Gnomad4 SAS exome AF: 0.0000116

Gnomad4 FIN exome AF: 0.00

Gnomad4 NFE exome AF: 0.00000719

Gnomad4 OTH exome AF: 0.0000166

GnomAD4 genome Cov.: 32

Alfa AF: 0.0000329 Hom.: 0

Bravo AF: 0.0000113

ClinVar

Significance: Likely benign

Submissions summary: Benign:1

Revision: criteria provided, single submitter

Submissions by phenotype

Charcot-Marie-Tooth disease type 2 Benign:1

Oct 21, 2024

Labcorp Genetics (formerly Invitae), Labcorp

Significance: Likely benign

Review Status: criteria provided, single submitter

Collection Method: clinical testing

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Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.77
CADD	Benign	2.4
DANN	Benign	0.71

Splicing

Name	Calibrated prediction	Score	Prediction
dbscSNV1_ADA	Benign	0.00044
dbscSNV1_RF	Benign	0.016
SpliceAI score (max)		0.020		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: rs374795892; hg19: chr7-30662085;