rs2233805

Positions:

• chr16-75647244-T-C

Variant summary

Our verdict is Benign. Variant got -12 ACMG points: 0P and 12B. BP4_Strong BA1

The NM_005548.3(KARS1):​c.62+334A>G variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.095 in 152,306 control chromosomes in the GnomAD database, including 1,247 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 0.095 (1247 hom., cov: 32)
• Consequence: KARS1 NM_005548.3 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.618

Genes affected

KARS1 (HGNC:6215): (lysyl-tRNA synthetase 1) Aminoacyl-tRNA synthetases are a class of enzymes that charge tRNAs with their cognate amino acids. Lysyl-tRNA synthetase is a homodimer localized to the cytoplasm which belongs to the class II family of tRNA synthetases. It has been shown to be a target of autoantibodies in the human autoimmune diseases, polymyositis or dermatomyositis. Alternatively spliced transcript variants encoding different isoforms have been found for this gene. [provided by RefSeq, Jul 2008]

KARS1 (HGNC:):

ACMG classification

Verdict is Benign. Variant got -12 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.9).
• BA1: GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.229 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
KARS1	NM_005548.3	c.62+334A>G		intron_variant		ENST00000302445.8	NP_005539.1
KARS1	NM_001130089.2	c.-35+334A>G		intron_variant			NP_001123561.1
KARS1	NM_001378148.1	c.-407+220A>G		intron_variant			NP_001365077.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
KARS1	ENST00000302445.8	c.62+334A>G		intron_variant		1	NM_005548.3	ENSP00000303043.3

Frequencies

GnomAD3 genomes AF: 0.0950 AC: 14452 AN: 152188 Hom.: 1245 Cov.: 32

Gnomad AFR AF: 0.233

Gnomad AMI AF: 0.0219

Gnomad AMR AF: 0.0396

Gnomad ASJ AF: 0.0421

Gnomad EAS AF: 0.0146

Gnomad SAS AF: 0.0499

Gnomad FIN AF: 0.0651

Gnomad MID AF: 0.0348

Gnomad NFE AF: 0.0421

Gnomad OTH AF: 0.0664

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

GnomAD4 genome AF: 0.0950 AC: 14471 AN: 152306 Hom.: 1247 Cov.: 32 AF XY: 0.0923 AC XY: 6875 AN XY: 74492

Gnomad4 AFR AF: 0.233

Gnomad4 AMR AF: 0.0396

Gnomad4 ASJ AF: 0.0421

Gnomad4 EAS AF: 0.0143

Gnomad4 SAS AF: 0.0501

Gnomad4 FIN AF: 0.0651

Gnomad4 NFE AF: 0.0421

Gnomad4 OTH AF: 0.0658

Alfa AF: 0.0489 Hom.: 505

Bravo AF: 0.0991

Asia WGS AF: 0.0510 AC: 179 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.90
CADD	Benign	2.3
DANN	Benign	0.34

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

Publications

LitVar

Other links and lift over

dbSNP: rs2233805; hg19: chr16-75681142;