NM_001014437.3:c.1031+89G>A

Variant names:

• chr11-3028907-C-T
• rs2071101
• NM_001014437.3:c.1031+89G>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.1031+89G>A variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0316 in 908,756 control chromosomes in the GnomAD database, including 4,630 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 0.025 (533 hom., cov: 32)
  • Exomes 𝑓: 0.033 (4097 hom.)
• Consequence: CARS1 NM_001014437.3 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 1.36
• Publications: 8 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=-0.77).
• BA1: GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.416 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.1031+89G>A		intron	N/A	NP_001014437.1	P49589-3
	CARS1	NM_001194997.2		c.1031+89G>A		intron	N/A	NP_001181926.1
	CARS1	NM_001751.6		c.782+89G>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.1031+89G>A		intron	N/A	ENSP00000369897.4	P49589-3
	CARS1	ENST00000397111.9	TSL:1	c.782+89G>A		intron	N/A	ENSP00000380300.5	P49589-1
	CARS1	ENST00000278224.13	TSL:1	c.782+89G>A		intron	N/A	ENSP00000278224.9	P49589-2

Frequencies

GnomAD3 genomes AF: 0.0249 AC: 3783 AN: 152164 Hom.: 533 Cov.: 32

Gnomad AFR AF: 0.00417

Gnomad AMI AF: 0.00

Gnomad AMR AF: 0.0623

Gnomad ASJ AF: 0.00202

Gnomad EAS AF: 0.430

Gnomad SAS AF: 0.0573

Gnomad FIN AF: 0.00

Gnomad MID AF: 0.00633

Gnomad NFE AF: 0.00154

Gnomad OTH AF: 0.0244

GnomAD4 exome AF: 0.0330 AC: 24941 AN: 756474 Hom.: 4097 Cov.: 10 AF XY: 0.0324 AC XY: 12909 AN XY: 398478

African (AFR) AF: 0.00349 AC: 68 AN: 19504

American (AMR) AF: 0.0924 AC: 3484 AN: 37712

Ashkenazi Jewish (ASJ) AF: 0.00291 AC: 57 AN: 19584

East Asian (EAS) AF: 0.445 AC: 16174 AN: 36342

South Asian (SAS) AF: 0.0458 AC: 3081 AN: 67296

European-Finnish (FIN) AF: 0.000332 AC: 17 AN: 51250

Middle Eastern (MID) AF: 0.00501 AC: 14 AN: 2794

European-Non Finnish (NFE) AF: 0.00163 AC: 792 AN: 485230

Other (OTH) AF: 0.0341 AC: 1254 AN: 36762

GnomAD4 genome AF: 0.0249 AC: 3785 AN: 152282 Hom.: 533 Cov.: 32 AF XY: 0.0280 AC XY: 2084 AN XY: 74456

African (AFR) AF: 0.00416 AC: 173 AN: 41562

American (AMR) AF: 0.0623 AC: 954 AN: 15302

Ashkenazi Jewish (ASJ) AF: 0.00202 AC: 7 AN: 3472

East Asian (EAS) AF: 0.431 AC: 2217 AN: 5144

South Asian (SAS) AF: 0.0565 AC: 273 AN: 4832

European-Finnish (FIN) AF: 0.00 AC: 0 AN: 10624

Middle Eastern (MID) AF: 0.00680 AC: 2 AN: 294

European-Non Finnish (NFE) AF: 0.00154 AC: 105 AN: 68028

Other (OTH) AF: 0.0255 AC: 54 AN: 2114

Alfa AF: 0.00821 Hom.: 8

Bravo AF: 0.0304

Asia WGS AF: 0.203 AC: 703 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.77
CADD	Benign	9.2
DANN	Benign	0.86
PhyloP100		1.4
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: rs2071101; hg19: chr11-3050137; COSMIC: COSV53450338; COSMIC: COSV53450338;