11-3015094-C-T

Variant names:

• chr11-3015094-C-T
• rs739401
• NM_001014437.3:c.1986+687G>A

Variant summary

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

The NM_001014437.3(CARS1):​c.1986+687G>A variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.451 in 152,076 control chromosomes in the GnomAD database, including 16,231 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 0.45 (16231 hom., cov: 33)
• Consequence: CARS1 NM_001014437.3 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -1.64
• Publications: 29 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=-0.91).
• BA1: GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.619 is higher than 0.05.

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_001014437.3. You can select a different transcript below to see updated ACMG assignments.

RefSeq Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	CARS1	NM_001014437.3	MANE Select	c.1986+687G>A		intron	N/A	NP_001014437.1	P49589-3
	CARS1	NM_001194997.2		c.1986+687G>A		intron	N/A	NP_001181926.1
	CARS1	NM_001751.6		c.1737+687G>A		intron	N/A	NP_001742.1	P49589-1

Ensembl Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	CARS1	ENST00000380525.9	TSL:1 MANE Select	c.1986+687G>A		intron	N/A	ENSP00000369897.4	P49589-3
	CARS1	ENST00000397111.9	TSL:1	c.1737+687G>A		intron	N/A	ENSP00000380300.5	P49589-1
	CARS1	ENST00000278224.13	TSL:1	c.1737+687G>A		intron	N/A	ENSP00000278224.9	P49589-2

Frequencies

GnomAD3 genomes AF: 0.451 AC: 68532 AN: 151956 Hom.: 16211 Cov.: 33

Gnomad AFR AF: 0.312

Gnomad AMI AF: 0.570

Gnomad AMR AF: 0.563

Gnomad ASJ AF: 0.511

Gnomad EAS AF: 0.637

Gnomad SAS AF: 0.493

Gnomad FIN AF: 0.385

Gnomad MID AF: 0.484

Gnomad NFE AF: 0.498

Gnomad OTH AF: 0.480

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

GnomAD4 genome AF: 0.451 AC: 68587 AN: 152076 Hom.: 16231 Cov.: 33 AF XY: 0.451 AC XY: 33501 AN XY: 74342

African (AFR) AF: 0.312 AC: 12954 AN: 41474

American (AMR) AF: 0.564 AC: 8612 AN: 15272

Ashkenazi Jewish (ASJ) AF: 0.511 AC: 1774 AN: 3470

East Asian (EAS) AF: 0.637 AC: 3300 AN: 5178

South Asian (SAS) AF: 0.493 AC: 2380 AN: 4826

European-Finnish (FIN) AF: 0.385 AC: 4070 AN: 10572

Middle Eastern (MID) AF: 0.486 AC: 143 AN: 294

European-Non Finnish (NFE) AF: 0.497 AC: 33812 AN: 67964

Other (OTH) AF: 0.483 AC: 1022 AN: 2114

Alfa AF: 0.481 Hom.: 26643

Bravo AF: 0.459

Asia WGS AF: 0.544 AC: 1895 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.91
CADD	Benign	0.24
DANN	Benign	0.33
PhyloP100		-1.6
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: rs739401; hg19: chr11-3036324;