chr11-3044070-G-A

Variant names:

• chr11-3044070-G-A
• rs375579
• NM_001014437.3:c.275-1814C>T

Variant summary

Our verdict is Likely benign. The variant received -2 ACMG points: 2P and 4B. PM2 BP4_Strong

The NM_001014437.3(CARS1):​c.275-1814C>T variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00000658 in 151,940 control chromosomes in the GnomAD database, with no homozygous occurrence. 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 0.0000066 (0 hom., cov: 31)
• Consequence: CARS1 NM_001014437.3 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -1.69
• 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: Likely_benign. The variant received -2 ACMG points.

• PM2: Very rare variant in population databases, with high coverage
• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.9).

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

Selected	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	CARS1	NM_001014437.3	MANE Select	c.275-1814C>T		intron	N/A	NP_001014437.1
	CARS1	NM_001194997.2		c.275-1814C>T		intron	N/A	NP_001181926.1
	CARS1	NM_001751.6		c.26-1814C>T		intron	N/A	NP_001742.1

Ensembl Transcripts

Selected	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	CARS1	ENST00000380525.9	TSL:1 MANE Select	c.275-1814C>T		intron	N/A	ENSP00000369897.4
	CARS1	ENST00000397111.9	TSL:1	c.26-1814C>T		intron	N/A	ENSP00000380300.5
	CARS1	ENST00000278224.13	TSL:1	c.26-1814C>T		intron	N/A	ENSP00000278224.9

Frequencies

GnomAD3 genomes AF: 0.00000658 AC: 1 AN: 151940 Hom.: 0 Cov.: 31

Gnomad AFR AF: 0.0000242

Gnomad AMI AF: 0.00

Gnomad AMR AF: 0.00

Gnomad ASJ AF: 0.00

Gnomad EAS AF: 0.00

Gnomad SAS AF: 0.00

Gnomad FIN AF: 0.00

Gnomad MID AF: 0.00

Gnomad NFE AF: 0.00

Gnomad OTH AF: 0.00

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

GnomAD4 genome AF: 0.00000658 AC: 1 AN: 151940 Hom.: 0 Cov.: 31 AF XY: 0.00 AC XY: 0 AN XY: 74196

African (AFR) AF: 0.0000242 AC: 1 AN: 41376

American (AMR) AF: 0.00 AC: 0 AN: 15264

Ashkenazi Jewish (ASJ) AF: 0.00 AC: 0 AN: 3468

East Asian (EAS) AF: 0.00 AC: 0 AN: 5160

South Asian (SAS) AF: 0.00 AC: 0 AN: 4826

European-Finnish (FIN) AF: 0.00 AC: 0 AN: 10556

Middle Eastern (MID) AF: 0.00 AC: 0 AN: 316

European-Non Finnish (NFE) AF: 0.00 AC: 0 AN: 67976

Other (OTH) AF: 0.00 AC: 0 AN: 2088

Alfa AF: 0.00 Hom.: 464

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.90
CADD	Benign	0.53
DANN	Benign	0.43
PhyloP100		-1.7
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

Other links and lift over

dbSNP: rs375579; hg19: chr11-3065300;