NM_001014437.3:c.26-3211A>G

Variant names:

• chr11-3051212-T-C
• rs6578318
• NM_001014437.3:c.26-3211A>G

Variant summary

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

The NM_001014437.3(CARS1):​c.26-3211A>G variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.927 in 152,350 control chromosomes in the GnomAD database, including 65,509 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 0.93 (65509 hom., cov: 35)
• Consequence: CARS1 NM_001014437.3 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.0160
• Publications: 4 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 Gene-Disease associations (from GenCC):

• microcephaly, developmental delay, and brittle hair syndrome

  Inheritance: AR Classification: STRONG, MODERATE Submitted by: G2P, Ambry Genetics

ACMG classification

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

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.92).
• BA1: GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.947 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
CARS1	NM_001014437.3	c.26-3211A>G		intron_variant	Intron 1 of 22	ENST00000380525.9	NP_001014437.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
CARS1	ENST00000380525.9	c.26-3211A>G		intron_variant	Intron 1 of 22	1	NM_001014437.3	ENSP00000369897.4

Frequencies

GnomAD3 genomes AF: 0.927 AC: 141112 AN: 152232 Hom.: 65463 Cov.: 35

Gnomad AFR AF: 0.956

Gnomad AMI AF: 0.973

Gnomad AMR AF: 0.944

Gnomad ASJ AF: 0.931

Gnomad EAS AF: 0.866

Gnomad SAS AF: 0.918

Gnomad FIN AF: 0.882

Gnomad MID AF: 0.943

Gnomad NFE AF: 0.917

Gnomad OTH AF: 0.925

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

GnomAD4 genome AF: 0.927 AC: 141216 AN: 152350 Hom.: 65509 Cov.: 35 AF XY: 0.925 AC XY: 68878 AN XY: 74492

African (AFR) AF: 0.955 AC: 39734 AN: 41592

American (AMR) AF: 0.944 AC: 14450 AN: 15304

Ashkenazi Jewish (ASJ) AF: 0.931 AC: 3233 AN: 3472

East Asian (EAS) AF: 0.866 AC: 4480 AN: 5176

South Asian (SAS) AF: 0.918 AC: 4437 AN: 4832

European-Finnish (FIN) AF: 0.882 AC: 9365 AN: 10618

Middle Eastern (MID) AF: 0.942 AC: 277 AN: 294

European-Non Finnish (NFE) AF: 0.917 AC: 62395 AN: 68036

Other (OTH) AF: 0.926 AC: 1958 AN: 2114

Alfa AF: 0.923 Hom.: 13142

Bravo AF: 0.931

Asia WGS AF: 0.908 AC: 3156 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.92
CADD	Benign	3.0
DANN	Benign	0.79
PhyloP100		-0.016
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: rs6578318; hg19: chr11-3072442;