chr9-92293147-A-T

Position:

• chr9-92293147-A-T

Variant summary

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

The NM_002161.6(IARS1):​c.-8+464T>A variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.408 in 152,092 control chromosomes in the GnomAD database, including 14,898 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 0.41 (14898 hom., cov: 32)
• Consequence: IARS1 NM_002161.6 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 0.280

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=-0.83).
• BA1: GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.658 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
IARS1	NM_002161.6	c.-8+464T>A		intron_variant		ENST00000443024.7	NP_002152.2

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
IARS1	ENST00000443024.7	c.-8+464T>A		intron_variant		5	NM_002161.6	ENSP00000406448	P1

Frequencies

GnomAD3 genomes AF: 0.408 AC: 61978 AN: 151974 Hom.: 14882 Cov.: 32

Gnomad AFR AF: 0.665

Gnomad AMI AF: 0.525

Gnomad AMR AF: 0.296

Gnomad ASJ AF: 0.379

Gnomad EAS AF: 0.107

Gnomad SAS AF: 0.223

Gnomad FIN AF: 0.278

Gnomad MID AF: 0.563

Gnomad NFE AF: 0.333

Gnomad OTH AF: 0.393

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

GnomAD4 genome AF: 0.408 AC: 62032 AN: 152092 Hom.: 14898 Cov.: 32 AF XY: 0.398 AC XY: 29608 AN XY: 74320

Gnomad4 AFR AF: 0.665

Gnomad4 AMR AF: 0.295

Gnomad4 ASJ AF: 0.379

Gnomad4 EAS AF: 0.108

Gnomad4 SAS AF: 0.221

Gnomad4 FIN AF: 0.278

Gnomad4 NFE AF: 0.333

Gnomad4 OTH AF: 0.387

Alfa AF: 0.378 Hom.: 1615

Bravo AF: 0.423

Asia WGS AF: 0.181 AC: 627 AN: 3474

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.83
CADD	Benign	6.9
DANN	Benign	0.78

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: rs10820966; hg19: chr9-95055429;