1-32775529-CCCTTT-C

Position:

• chr1-32775529-CCCTTT-C

Variant summary

Our verdict is Benign. Variant got -10 ACMG points: 0P and 10B. BP6_Moderate BS1 BS2

The NM_003680.4(YARS1):​c.*447_*451del variant causes a 3 prime UTR change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00946 in 179,400 control chromosomes in the GnomAD database, including 18 homozygotes. Variant has been reported in ClinVar as Likely benign (★).

• Frequency:
  • Genomes: 𝑓 0.0092 (12 hom., cov: 32)
  • Exomes 𝑓: 0.011 (6 hom.)
• Consequence: YARS1 NM_003680.4 3_prime_UTR
• Clinical Significance: Likely benign criteria provided, single submitter B:1
• Conservation: PhyloP100: 1.62

Genes affected

YARS1 (HGNC:12840): (tyrosyl-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. Tyrosyl-tRNA synthetase belongs to the class I tRNA synthetase family. Cytokine activities have also been observed for the human tyrosyl-tRNA synthetase, after it is split into two parts, an N-terminal fragment that harbors the catalytic site and a C-terminal fragment found only in the mammalian enzyme. The N-terminal fragment is an interleukin-8-like cytokine, whereas the released C-terminal fragment is an EMAP II-like cytokine. [provided by RefSeq, Jul 2008]

ACMG classification

Verdict is Benign. Variant got -10 ACMG points.

• BP6: Variant 1-32775529-CCCTTT-C is Benign according to our data. Variant chr1-32775529-CCCTTT-C is described in ClinVar as [Likely_benign]. Clinvar id is 297138.Status of the report is criteria_provided_single_submitter, 1 stars.
• BS1: Variant frequency is greater than expected in population sas. gnomad4 allele frequency = 0.00923 (1405/152298) while in subpopulation SAS AF= 0.0325 (157/4826). AF 95% confidence interval is 0.0284. There are 12 homozygotes in gnomad4. There are 762 alleles in male gnomad4 subpopulation. Median coverage is 32. This position pass quality control queck.
• BS2: High Homozygotes in GnomAd4 at 12 AR gene

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
YARS1	NM_003680.4	c.*447_*451del		3_prime_UTR_variant	13/13	ENST00000373477.9	NP_003671.1
YARS1	XM_011542347.3	c.*447_*451del		3_prime_UTR_variant	11/11		XP_011540649.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
YARS1	ENST00000373477.9	c.*447_*451del		3_prime_UTR_variant	13/13	1	NM_003680.4	ENSP00000362576	P1

Frequencies

GnomAD3 genomes AF: 0.00922 AC: 1403 AN: 152180 Hom.: 12 Cov.: 32

Gnomad AFR AF: 0.00159

Gnomad AMI AF: 0.00

Gnomad AMR AF: 0.00609

Gnomad ASJ AF: 0.0181

Gnomad EAS AF: 0.00

Gnomad SAS AF: 0.0321

Gnomad FIN AF: 0.0199

Gnomad MID AF: 0.00

Gnomad NFE AF: 0.0118

Gnomad OTH AF: 0.00669

GnomAD4 exome AF: 0.0108 AC: 293 AN: 27102 Hom.: 6 AF XY: 0.0131 AC XY: 186 AN XY: 14172

Gnomad4 AFR exome AF: 0.00

Gnomad4 AMR exome AF: 0.00503

Gnomad4 ASJ exome AF: 0.0130

Gnomad4 EAS exome AF: 0.00

Gnomad4 SAS exome AF: 0.0350

Gnomad4 FIN exome AF: 0.0154

Gnomad4 NFE exome AF: 0.00810

Gnomad4 OTH exome AF: 0.0144

GnomAD4 genome AF: 0.00923 AC: 1405 AN: 152298 Hom.: 12 Cov.: 32 AF XY: 0.0102 AC XY: 762 AN XY: 74476

Gnomad4 AFR AF: 0.00159

Gnomad4 AMR AF: 0.00608

Gnomad4 ASJ AF: 0.0181

Gnomad4 EAS AF: 0.00

Gnomad4 SAS AF: 0.0325

Gnomad4 FIN AF: 0.0199

Gnomad4 NFE AF: 0.0118

Gnomad4 OTH AF: 0.00662

Alfa AF: 0.0113 Hom.: 1

Bravo AF: 0.00743

ClinVar

Significance: Likely benign

Submissions summary: Benign:1

Revision: criteria provided, single submitter

Submissions by phenotype

Charcot-Marie-Tooth, Intermediate Benign:1

Likely benign, criteria provided, single submitter

clinical testing

Illumina Laboratory Services, Illumina

Jun 14, 2016

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Computational scores

Source: dbNSFP v4.3

Splicing

Find out detailed SpliceAI scores and Pangolin per-transcript scores at spliceailookup.broadinstitute.org

Publications

LitVar

Other links and lift over

dbSNP: rs142185532; hg19: chr1-33241130;