11-3044070-G-C

Position:

• chr11-3044070-G-C

Variant summary

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

The ENST00000380525.9(CARS1):​c.275-1814C>G variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.329 in 152,004 control chromosomes in the GnomAD database, including 10,296 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 (10296 hom., cov: 31)
• Consequence: CARS1 ENST00000380525.9 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -1.69

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 = 0.639 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
CARS1	NM_001014437.3	c.275-1814C>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.275-1814C>G		intron_variant		1	NM_001014437.3	ENSP00000369897	P3

Frequencies

GnomAD3 genomes AF: 0.329 AC: 49945 AN: 151886 Hom.: 10288 Cov.: 31

Gnomad AFR AF: 0.0862

Gnomad AMI AF: 0.545

Gnomad AMR AF: 0.483

Gnomad ASJ AF: 0.430

Gnomad EAS AF: 0.658

Gnomad SAS AF: 0.431

Gnomad FIN AF: 0.317

Gnomad MID AF: 0.351

Gnomad NFE AF: 0.403

Gnomad OTH AF: 0.352

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

GnomAD4 genome AF: 0.329 AC: 49961 AN: 152004 Hom.: 10296 Cov.: 31 AF XY: 0.331 AC XY: 24567 AN XY: 74304

Gnomad4 AFR AF: 0.0861

Gnomad4 AMR AF: 0.484

Gnomad4 ASJ AF: 0.430

Gnomad4 EAS AF: 0.658

Gnomad4 SAS AF: 0.429

Gnomad4 FIN AF: 0.317

Gnomad4 NFE AF: 0.403

Gnomad4 OTH AF: 0.357

Alfa AF: 0.201 Hom.: 464

Bravo AF: 0.331

Asia WGS AF: 0.521 AC: 1812 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	0.24
DANN	Benign	0.49
RBP_binding_hub_radar		0.67
RBP_regulation_power_radar		2.0

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: rs375579; hg19: chr11-3065300; COSMIC: COSV53460966; COSMIC: COSV53460966;