rs7205918

Variant names:

• chr16-70254829-T-C
• rs7205918
• NM_001605.3:c.2287-95A>G

Your query was ambiguous. Multiple possible variants found:

• chr16-70254829-T-C
• chr16-70254829-T-G

Variant summary

Our verdict is Benign. Variant got -20 ACMG points: 0P and 20B. BP4_Strong BP6_Very_Strong BA1

The NM_001605.3(AARS1):​c.2287-95A>G variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0258 in 812,416 control chromosomes in the GnomAD database, including 2,943 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★★).

• Frequency:
  • Genomes: 𝑓 0.090 (2036 hom., cov: 32)
  • Exomes 𝑓: 0.011 (907 hom.)
• Consequence: AARS1 NM_001605.3 intron
• Clinical Significance: Benign criteria provided, multiple submitters, no conflicts B:2
• Conservation: PhyloP100: -1.61

Genes affected

AARS1 (HGNC:20): (alanyl-tRNA synthetase 1) The human alanyl-tRNA synthetase (AARS) belongs to a family of tRNA synthases, of the class II enzymes. Class II tRNA synthases evolved early in evolution and are highly conserved. This is reflected by the fact that 498 of the 968-residue polypeptide human AARS shares 41% identity witht the E.coli protein. tRNA synthases are the enzymes that interpret the RNA code and attach specific aminoacids to the tRNAs that contain the cognate trinucleotide anticodons. They consist of a catalytic domain which interacts with the amino acid acceptor-T psi C helix of the tRNA, and a second domain which interacts with the rest of the tRNA structure. [provided by RefSeq, Jul 2008]

ACMG classification

Verdict is Benign. Variant got -20 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.91).
• BP6: Variant 16-70254829-T-C is Benign according to our data. Variant chr16-70254829-T-C is described in ClinVar as [Benign]. Clinvar id is 676184.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars.
• BA1: GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.306 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
AARS1	NM_001605.3	c.2287-95A>G		intron_variant	Intron 16 of 20	ENST00000261772.13	NP_001596.2
AARS1	XM_047433666.1	c.2102-95A>G		intron_variant	Intron 15 of 15		XP_047289622.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
AARS1	ENST00000261772.13	c.2287-95A>G		intron_variant	Intron 16 of 20	1	NM_001605.3	ENSP00000261772.8

Frequencies

GnomAD3 genomes AF: 0.0900 AC: 13698 AN: 152126 Hom.: 2026 Cov.: 32

Gnomad AFR AF: 0.310

Gnomad AMI AF: 0.0439

Gnomad AMR AF: 0.0380

Gnomad ASJ AF: 0.00

Gnomad EAS AF: 0.000193

Gnomad SAS AF: 0.00269

Gnomad FIN AF: 0.00

Gnomad MID AF: 0.0222

Gnomad NFE AF: 0.00104

Gnomad OTH AF: 0.0676

GnomAD4 exome AF: 0.0109 AC: 7222 AN: 660174 Hom.: 907 AF XY: 0.00904 AC XY: 3178 AN XY: 351398

Gnomad4 AFR exome AF: 0.299

Gnomad4 AMR exome AF: 0.0164

Gnomad4 ASJ exome AF: 0.0000490

Gnomad4 EAS exome AF: 0.0000914

Gnomad4 SAS exome AF: 0.00248

Gnomad4 FIN exome AF: 0.0000232

Gnomad4 NFE exome AF: 0.000817

Gnomad4 OTH exome AF: 0.0241

GnomAD4 genome AF: 0.0903 AC: 13742 AN: 152242 Hom.: 2036 Cov.: 32 AF XY: 0.0871 AC XY: 6482 AN XY: 74452

Gnomad4 AFR AF: 0.310

Gnomad4 AMR AF: 0.0380

Gnomad4 ASJ AF: 0.00

Gnomad4 EAS AF: 0.000193

Gnomad4 SAS AF: 0.00207

Gnomad4 FIN AF: 0.00

Gnomad4 NFE AF: 0.00104

Gnomad4 OTH AF: 0.0693

Alfa AF: 0.0346 Hom.: 117

Bravo AF: 0.101

Asia WGS AF: 0.0320 AC: 111 AN: 3478

ClinVar

Significance: Benign

Submissions summary: Benign:2

Revision: criteria provided, multiple submitters, no conflicts

Submissions by phenotype

not provided Benign:2

-

Breakthrough Genomics, Breakthrough Genomics

Significance: Benign

Review Status: criteria provided, single submitter

Collection Method: not provided

- -

Jun 16, 2018

GeneDx

Significance: Benign

Review Status: criteria provided, single submitter

Collection Method: clinical testing

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	-0.91
CADD	Benign	0.053
DANN	Benign	0.35
RBP_binding_hub_radar		0.0
RBP_regulation_power_radar		1.3

Splicing

Name	Calibrated prediction	Score	Prediction
SpliceAI score (max)		0.18		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: rs7205918; hg19: chr16-70288732;