rs8053257

chr16-75640790-G-Achr16-75640790-G-C

Variant summary

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

The NM_005548.3(KARS1):c.223-441C>T variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.178 in 152,216 control chromosomes in the GnomAD database, including 5,027 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 0.18 (5027 hom., cov: 32)
• Consequence: KARS1 NM_005548.3 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.272

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]

ACMG classification

Verdict is Benign. Variant got -12 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.82).
• BA1: GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.471 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
KARS1	NM_005548.3	c.223-441C>T		intron_variant		ENST00000302445.8
KARS1	NM_001130089.2	c.307-441C>T		intron_variant
KARS1	NM_001378148.1	c.-246-441C>T		intron_variant

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
KARS1	ENST00000302445.8	c.223-441C>T		intron_variant		1	NM_005548.3	A1

Frequencies

GnomAD3 genomes AF: 0.178 AC: 27012 AN: 152098 Hom.: 5019 Cov.: 32

Gnomad AFR AF: 0.477

Gnomad AMI AF: 0.0592

Gnomad AMR AF: 0.0794

Gnomad ASJ AF: 0.0737

Gnomad EAS AF: 0.0337

Gnomad SAS AF: 0.107

Gnomad FIN AF: 0.0711

Gnomad MID AF: 0.0949

Gnomad NFE AF: 0.0590

Gnomad OTH AF: 0.134

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

GnomAD4 genome AF: 0.178 AC: 27056 AN: 152216 Hom.: 5027 Cov.: 32 AF XY: 0.173 AC XY: 12854 AN XY: 74440

Gnomad4 AFR AF: 0.477

Gnomad4 AMR AF: 0.0792

Gnomad4 ASJ AF: 0.0737

Gnomad4 EAS AF: 0.0335

Gnomad4 SAS AF: 0.106

Gnomad4 FIN AF: 0.0711

Gnomad4 NFE AF: 0.0590

Gnomad4 OTH AF: 0.133

Alfa AF: 0.0749 Hom.: 1264

Bravo AF: 0.190

Asia WGS AF: 0.117 AC: 406 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.82
Cadd	Benign	1.8
Dann	Benign	0.40

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: rs8053257; hg19: chr16-75674688;