5-140688193-T-C

Position:

• chr5-140688193-T-C

Variant summary

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

The NM_002109.6(HARS1):​c.180+2662A>G variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.211 in 151,892 control chromosomes in the GnomAD database, including 3,396 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 0.21 (3396 hom., cov: 32)
• Consequence: HARS1 NM_002109.6 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 0.220

Genes affected

HARS1 (HGNC:4816): (histidyl-tRNA synthetase 1) Aminoacyl-tRNA synthetases are a class of enzymes that charge tRNAs with their cognate amino acids. The protein encoded by this gene is a cytoplasmic enzyme which belongs to the class II family of aminoacyl-tRNA synthetases. The enzyme is responsible for the synthesis of histidyl-transfer RNA, which is essential for the incorporation of histidine into proteins. The gene is located in a head-to-head orientation with HARSL on chromosome five, where the homologous genes share a bidirectional promoter. The gene product is a frequent target of autoantibodies in the human autoimmune disease polymyositis/dermatomyositis. Several transcript variants encoding different isoforms have been found for this gene. [provided by RefSeq, Apr 2012]

ACMG classification

Verdict is Benign. Variant got -12 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.78).
• BA1: GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.214 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
HARS1	NM_002109.6	c.180+2662A>G		intron_variant		ENST00000504156.7

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
HARS1	ENST00000504156.7	c.180+2662A>G		intron_variant		1	NM_002109.6	P3

Frequencies

GnomAD3 genomes AF: 0.211 AC: 31971 AN: 151774 Hom.: 3397 Cov.: 32

Gnomad AFR AF: 0.218

Gnomad AMI AF: 0.156

Gnomad AMR AF: 0.190

Gnomad ASJ AF: 0.240

Gnomad EAS AF: 0.160

Gnomad SAS AF: 0.178

Gnomad FIN AF: 0.266

Gnomad MID AF: 0.146

Gnomad NFE AF: 0.209

Gnomad OTH AF: 0.191

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

GnomAD4 genome AF: 0.211 AC: 31982 AN: 151892 Hom.: 3396 Cov.: 32 AF XY: 0.214 AC XY: 15858 AN XY: 74244

Gnomad4 AFR AF: 0.217

Gnomad4 AMR AF: 0.189

Gnomad4 ASJ AF: 0.240

Gnomad4 EAS AF: 0.160

Gnomad4 SAS AF: 0.178

Gnomad4 FIN AF: 0.266

Gnomad4 NFE AF: 0.209

Gnomad4 OTH AF: 0.192

Alfa AF: 0.206 Hom.: 621

Bravo AF: 0.204

Asia WGS AF: 0.187 AC: 649 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.78
CADD	Benign	7.2
DANN	Benign	0.87

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: rs801186; hg19: chr5-140067778;