11-3039495-A-G

Variant names:

• chr11-3039495-A-G
• rs451041
• NM_001014437.3:c.553-203T>C

Variant summary

Our verdict is Benign. The variant received -12 ACMG points: 0P and 12B. BP4_Strong BA1

The NM_001014437.3(CARS1):​c.553-203T>C variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.51 in 151,954 control chromosomes in the GnomAD database, including 20,028 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 0.51 (20028 hom., cov: 32)
• Consequence: CARS1 NM_001014437.3 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -2.69
• Publications: 35 publications found

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

Our verdict: Benign. The variant received -12 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.93).
• BA1: GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.657 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
CARS1	NM_001014437.3	c.553-203T>C		intron_variant	Intron 5 of 22	ENST00000380525.9	NP_001014437.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
CARS1	ENST00000380525.9	c.553-203T>C		intron_variant	Intron 5 of 22	1	NM_001014437.3	ENSP00000369897.4

Frequencies

GnomAD3 genomes AF: 0.510 AC: 77397 AN: 151836 Hom.: 20008 Cov.: 32

Gnomad AFR AF: 0.511

Gnomad AMI AF: 0.570

Gnomad AMR AF: 0.582

Gnomad ASJ AF: 0.512

Gnomad EAS AF: 0.675

Gnomad SAS AF: 0.502

Gnomad FIN AF: 0.387

Gnomad MID AF: 0.506

Gnomad NFE AF: 0.498

Gnomad OTH AF: 0.521

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

GnomAD4 genome AF: 0.510 AC: 77467 AN: 151954 Hom.: 20028 Cov.: 32 AF XY: 0.506 AC XY: 37596 AN XY: 74238

African (AFR) AF: 0.511 AC: 21183 AN: 41436

American (AMR) AF: 0.583 AC: 8903 AN: 15274

Ashkenazi Jewish (ASJ) AF: 0.512 AC: 1775 AN: 3466

East Asian (EAS) AF: 0.675 AC: 3478 AN: 5150

South Asian (SAS) AF: 0.502 AC: 2419 AN: 4820

European-Finnish (FIN) AF: 0.387 AC: 4089 AN: 10558

Middle Eastern (MID) AF: 0.507 AC: 149 AN: 294

European-Non Finnish (NFE) AF: 0.498 AC: 33848 AN: 67936

Other (OTH) AF: 0.523 AC: 1103 AN: 2108

Alfa AF: 0.504 Hom.: 59407

Bravo AF: 0.528

Asia WGS AF: 0.580 AC: 2019 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	0.13
DANN	Benign	0.33
PhyloP100		-2.7
Mutation Taster		=100/0	polymorphism (auto)

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

Other links and lift over

dbSNP: rs451041; hg19: chr11-3060725;