11-3034131-T-C

Variant summary

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

The NM_001014437.3(CARS1):c.801+3919A>G variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.464 in 151,980 control chromosomes in the GnomAD database, including 17,626 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 0.46 (17626 hom., cov: 31)
• Consequence: CARS1 NM_001014437.3 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 0.275

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-AS1 (HGNC:40125): (CARS1 antisense RNA 1)

ACMG classification

Verdict is Benign. Variant got -12 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.93).
• BA1: GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.646 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
CARS1	NM_001014437.3	c.801+3919A>G		intron_variant		ENST00000380525.9
CARS1-AS1	NR_046580.1	n.2183+2555T>C		intron_variant, non_coding_transcript_variant

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
CARS1	ENST00000380525.9	c.801+3919A>G		intron_variant		1	NM_001014437.3	P3
CARS1-AS1	ENST00000499962.1	n.2183+2555T>C		intron_variant, non_coding_transcript_variant		2

Frequencies

GnomAD3 genomes AF: 0.464 AC: 70505 AN: 151862 Hom.: 17610 Cov.: 31

Gnomad AFR AF: 0.652

Gnomad AMI AF: 0.396

Gnomad AMR AF: 0.366

Gnomad ASJ AF: 0.371

Gnomad EAS AF: 0.232

Gnomad SAS AF: 0.399

Gnomad FIN AF: 0.481

Gnomad MID AF: 0.424

Gnomad NFE AF: 0.399

Gnomad OTH AF: 0.425

We have no GnomAD4 exomes data on this position. Probably position not covered by the project.

GnomAD4 genome AF: 0.464 AC: 70558 AN: 151980 Hom.: 17626 Cov.: 31 AF XY: 0.463 AC XY: 34380 AN XY: 74268

Gnomad4 AFR AF: 0.652

Gnomad4 AMR AF: 0.365

Gnomad4 ASJ AF: 0.371

Gnomad4 EAS AF: 0.232

Gnomad4 SAS AF: 0.399

Gnomad4 FIN AF: 0.481

Gnomad4 NFE AF: 0.399

Gnomad4 OTH AF: 0.422

Alfa AF: 0.389 Hom.: 5189

Bravo AF: 0.463

Asia WGS AF: 0.345 AC: 1200 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.93
Cadd	Benign	1.2
Dann	Benign	0.60

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: rs572373; hg19: chr11-3055361;