11-3040762-T-C

Position:

• chr11-3040762-T-C

Variant summary

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

The NM_001378140.1(CARS1):​c.-385A>G variant causes a 5 prime UTR change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.394 in 886,214 control chromosomes in the GnomAD database, including 74,286 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 0.33 (10276 hom., cov: 32)
  • Exomes 𝑓: 0.41 (64010 hom.)
• Consequence: CARS1 NM_001378140.1 5_prime_UTR
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.364

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]

CARS1 (HGNC:):

ACMG classification

Verdict is Benign. Variant got -12 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.94).
• BA1: GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.641 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
CARS1	NM_001014437.3	c.455+134A>G		intron_variant		ENST00000380525.9	NP_001014437.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
CARS1	ENST00000380525.9	c.455+134A>G		intron_variant		1	NM_001014437.3	ENSP00000369897.4

Frequencies

GnomAD3 genomes AF: 0.328 AC: 49906 AN: 152006 Hom.: 10268 Cov.: 32

Gnomad AFR AF: 0.0866

Gnomad AMI AF: 0.545

Gnomad AMR AF: 0.482

Gnomad ASJ AF: 0.430

Gnomad EAS AF: 0.659

Gnomad SAS AF: 0.432

Gnomad FIN AF: 0.317

Gnomad MID AF: 0.351

Gnomad NFE AF: 0.401

Gnomad OTH AF: 0.352

GnomAD4 exome AF: 0.407 AC: 299078 AN: 734090 Hom.: 64010 Cov.: 10 AF XY: 0.408 AC XY: 154645 AN XY: 378972

Gnomad4 AFR exome AF: 0.0769

Gnomad4 AMR exome AF: 0.562

Gnomad4 ASJ exome AF: 0.411

Gnomad4 EAS exome AF: 0.674

Gnomad4 SAS exome AF: 0.414

Gnomad4 FIN exome AF: 0.322

Gnomad4 NFE exome AF: 0.401

Gnomad4 OTH exome AF: 0.393

GnomAD4 genome AF: 0.328 AC: 49925 AN: 152124 Hom.: 10276 Cov.: 32 AF XY: 0.330 AC XY: 24558 AN XY: 74370

Gnomad4 AFR AF: 0.0865

Gnomad4 AMR AF: 0.483

Gnomad4 ASJ AF: 0.430

Gnomad4 EAS AF: 0.659

Gnomad4 SAS AF: 0.430

Gnomad4 FIN AF: 0.317

Gnomad4 NFE AF: 0.401

Gnomad4 OTH AF: 0.357

Alfa AF: 0.383 Hom.: 5978

Bravo AF: 0.330

Asia WGS AF: 0.523 AC: 1818 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.94
CADD	Benign	2.2
DANN	Benign	0.53

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: rs369461; hg19: chr11-3061992;