rs7481584

Positions:

• chr11-3007859-G-A

Variant summary

Our verdict is Benign. Variant got -12 ACMG points: 0P and 12B. BP4_Strong BA1

The NM_001014437.3(CARS1):​c.2069-900C>T variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.278 in 152,174 control chromosomes in the GnomAD database, including 7,059 homozygotes. In-silico tool predicts a benign outcome for this variant. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar.

• Frequency:
  • Genomes: 𝑓 0.28 (7055 hom., cov: 32)
  • Exomes 𝑓: 0.33 (4 hom.)
• Consequence: CARS1 NM_001014437.3 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.453

Genes affected

CARS1 (HGNC:1493): (cysteinyl-tRNA synthetase 1) This gene encodes a class 1 aminoacyl-tRNA synthetase, cysteinyl-tRNA synthetase. Each of the twenty aminoacyl-tRNA synthetases catalyzes the aminoacylation of a specific tRNA or tRNA isoaccepting family with the cognate amino acid. This gene is one of several located near the imprinted gene domain on chromosome 11p15.5, an important tumor-suppressor gene region. Alterations in this region have been associated with Beckwith-Wiedemann syndrome, Wilms tumor, rhabdomyosarcoma, adrenocortical carcinoma, and lung, ovarian and breast cancers. Alternative splicing of this gene results in multiple transcript variants. [provided by RefSeq, Aug 2010]

ACMG classification

Verdict is Benign. Variant got -12 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.91).
• BA1: GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.611 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
CARS1	NM_001014437.3	c.2069-900C>T		intron_variant		ENST00000380525.9

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
CARS1	ENST00000380525.9	c.2069-900C>T		intron_variant		1	NM_001014437.3	P3

Frequencies

GnomAD3 genomes AF: 0.278 AC: 42217 AN: 151974 Hom.: 7042 Cov.: 32

Gnomad AFR AF: 0.137

Gnomad AMI AF: 0.481

Gnomad AMR AF: 0.443

Gnomad ASJ AF: 0.360

Gnomad EAS AF: 0.629

Gnomad SAS AF: 0.405

Gnomad FIN AF: 0.222

Gnomad MID AF: 0.307

Gnomad NFE AF: 0.291

Gnomad OTH AF: 0.306

GnomAD4 exome AF: 0.329 AC: 27 AN: 82 Hom.: 4 Cov.: 0 AF XY: 0.343 AC XY: 24 AN XY: 70

Gnomad4 ASJ exome AF: 0.750

Gnomad4 FIN exome AF: 0.167

Gnomad4 NFE exome AF: 0.297

Gnomad4 OTH exome AF: 0.500

GnomAD4 genome AF: 0.278 AC: 42246 AN: 152092 Hom.: 7055 Cov.: 32 AF XY: 0.281 AC XY: 20907 AN XY: 74342

Gnomad4 AFR AF: 0.137

Gnomad4 AMR AF: 0.444

Gnomad4 ASJ AF: 0.360

Gnomad4 EAS AF: 0.629

Gnomad4 SAS AF: 0.403

Gnomad4 FIN AF: 0.222

Gnomad4 NFE AF: 0.291

Gnomad4 OTH AF: 0.311

Alfa AF: 0.268 Hom.: 960

Bravo AF: 0.288

Asia WGS AF: 0.499 AC: 1734 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.91
CADD	Benign	1.4
DANN	Benign	0.29
RBP_binding_hub_radar		0.0
RBP_regulation_power_radar		1.2

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: rs7481584; hg19: chr11-3029089;