9-92247934-T-C

Position:

• chr9-92247934-T-C

Variant summary

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

The NM_002161.6(IARS1):​c.2617-383A>G variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.583 in 152,160 control chromosomes in the GnomAD database, including 28,397 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 0.58 (28397 hom., cov: 33)
• Consequence: IARS1 NM_002161.6 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -1.82

Genes affected

IARS1 (HGNC:5330): (isoleucyl-tRNA synthetase 1) Aminoacyl-tRNA synthetases catalyze the aminoacylation of tRNA by their cognate amino acid. Because of their central role in linking amino acids with nucleotide triplets contained in tRNAS, aminoacyl-tRNA synthetases are thought to be among the first proteins that appeared in evolution. Isoleucine-tRNA synthetase belongs to the class-I aminoacyl-tRNA synthetase family and has been identified as a target of autoantibodies in the autoimmune disease polymyositis/dermatomyositis. Alternatively spliced transcript variants have been found. [provided by RefSeq, Nov 2012]

ACMG classification

Verdict is Benign. Variant got -12 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.97).
• BA1: GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.85 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
IARS1	NM_002161.6	c.2617-383A>G		intron_variant		ENST00000443024.7	NP_002152.2

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
IARS1	ENST00000443024.7	c.2617-383A>G		intron_variant		5	NM_002161.6	ENSP00000406448	P1

Frequencies

GnomAD3 genomes AF: 0.583 AC: 88631 AN: 152042 Hom.: 28343 Cov.: 33

Gnomad AFR AF: 0.857

Gnomad AMI AF: 0.682

Gnomad AMR AF: 0.489

Gnomad ASJ AF: 0.516

Gnomad EAS AF: 0.212

Gnomad SAS AF: 0.518

Gnomad FIN AF: 0.461

Gnomad MID AF: 0.658

Gnomad NFE AF: 0.492

Gnomad OTH AF: 0.558

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

GnomAD4 genome AF: 0.583 AC: 88735 AN: 152160 Hom.: 28397 Cov.: 33 AF XY: 0.578 AC XY: 42965 AN XY: 74386

Gnomad4 AFR AF: 0.857

Gnomad4 AMR AF: 0.488

Gnomad4 ASJ AF: 0.516

Gnomad4 EAS AF: 0.213

Gnomad4 SAS AF: 0.517

Gnomad4 FIN AF: 0.461

Gnomad4 NFE AF: 0.492

Gnomad4 OTH AF: 0.552

Alfa AF: 0.522 Hom.: 9054

Bravo AF: 0.595

Asia WGS AF: 0.399 AC: 1387 AN: 3476

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.97
CADD	Benign	0.19
DANN	Benign	0.53

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: rs4743869; hg19: chr9-95010216;