chr7-30622471-T-A

Variant names:

• chr7-30622471-T-A
• NM_002047.4:c.1613+9T>A

Variant summary

Our verdict is Likely benign. Variant got -4 ACMG points: 2P and 6B. PM2 BP4_Strong BP6_Moderate

The NM_002047.4(GARS1):​c.1613+9T>A variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.000000684 in 1,461,696 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Likely benign (★).

• Frequency:
  • Genomes: not found (cov: 32)
  • Exomes 𝑓: 6.8e-7 (0 hom.)
• Consequence: GARS1 NM_002047.4 intron
• Clinical Significance: Likely benign criteria provided, single submitter B:1
• Conservation: PhyloP100: -0.0470

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 Likely_benign. Variant got -4 ACMG points.

• PM2: Very rare variant in population databases, with high coverage
• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.74).
• BP6: Variant 7-30622471-T-A is Benign according to our data. Variant chr7-30622471-T-A is described in ClinVar as [Likely_benign]. Clinvar id is 1160502.Status of the report is criteria_provided_single_submitter, 1 stars.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
GARS1	NM_002047.4	c.1613+9T>A		intron_variant	Intron 12 of 16	ENST00000389266.8	NP_002038.2
GARS1	NM_001316772.1	c.1451+9T>A		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+9T>A		intron_variant	Intron 12 of 16	1	NM_002047.4	ENSP00000373918.3
GARS1	ENST00000675651.1	c.1613+9T>A		intron_variant	Intron 12 of 16			ENSP00000502513.1
GARS1	ENST00000675810.1	c.1511+9T>A		intron_variant	Intron 11 of 15			ENSP00000502743.1
GARS1	ENST00000675693.1	c.1445+9T>A		intron_variant	Intron 13 of 17			ENSP00000502174.1
GARS1	ENST00000675051.1	c.1412+9T>A		intron_variant	Intron 12 of 16			ENSP00000502296.1
GARS1	ENST00000674815.1	c.1244+9T>A		intron_variant	Intron 12 of 16			ENSP00000502799.1
GARS1	ENST00000674851.1	c.1244+9T>A		intron_variant	Intron 13 of 17			ENSP00000502451.1
GARS1	ENST00000444666.6	n.1613+9T>A		intron_variant	Intron 12 of 17	3		ENSP00000415447.2
GARS1	ENST00000674616.1	n.*1327+9T>A		intron_variant	Intron 13 of 17			ENSP00000502408.1
GARS1	ENST00000674643.1	n.*713+9T>A		intron_variant	Intron 13 of 16			ENSP00000501636.1
GARS1	ENST00000674737.1	n.*951+9T>A		intron_variant	Intron 13 of 17			ENSP00000502464.1
GARS1	ENST00000674807.1	n.1613+9T>A		intron_variant	Intron 12 of 15			ENSP00000502814.1
GARS1	ENST00000675529.1	n.*1483+9T>A		intron_variant	Intron 13 of 17			ENSP00000501655.1
GARS1	ENST00000675859.1	n.1613+9T>A		intron_variant	Intron 12 of 14			ENSP00000502033.1
GARS1	ENST00000676088.1	n.*1555+9T>A		intron_variant	Intron 14 of 18			ENSP00000501884.1
GARS1	ENST00000676140.1	n.*558+9T>A		intron_variant	Intron 12 of 16			ENSP00000502571.1
GARS1	ENST00000676164.1	n.*1064+9T>A		intron_variant	Intron 12 of 16			ENSP00000501986.1
GARS1	ENST00000676210.1	n.*902+9T>A		intron_variant	Intron 13 of 17			ENSP00000502373.1
GARS1	ENST00000676259.1	n.*1045+9T>A		intron_variant	Intron 12 of 16			ENSP00000501980.1
GARS1	ENST00000676403.1	n.1613+9T>A		intron_variant	Intron 12 of 15			ENSP00000502681.1

Frequencies

GnomAD3 genomes Cov.: 32

GnomAD4 exome AF: 6.84e-7 AC: 1 AN: 1461696 Hom.: 0 Cov.: 31 AF XY: 0.00 AC XY: 0 AN XY: 727176

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: 0.00

Gnomad4 FIN exome AF: 0.00

Gnomad4 NFE exome AF: 8.99e-7

Gnomad4 OTH exome AF: 0.00

GnomAD4 genome Cov.: 32

ClinVar

Significance: Likely benign

Submissions summary: Benign:1

Revision: criteria provided, single submitter

Submissions by phenotype

Charcot-Marie-Tooth disease type 2 Benign:1

Feb 03, 2020

Labcorp Genetics (formerly Invitae), Labcorp

Significance: Likely benign

Review Status: criteria provided, single submitter

Collection Method: clinical testing

- -

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.74
CADD	Benign	1.9
DANN	Benign	0.77

Splicing

Name	Calibrated prediction	Score	Prediction
SpliceAI score (max)		0.010		Details are displayed if max score is > 0.2

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

Publications

No publications associated with this variant yet.

Other links and lift over

hg19: chr7-30662087;