rs112037794

Variant names:

• chr1-32775875-G-A
• rs112037794
• NM_003680.4:c.*106C>T

Your query was ambiguous. Multiple possible variants found:

• chr1-32775875-G-A
• chr1-32775875-G-T

Variant summary

Our verdict is Benign. The variant received -14 ACMG points: 0P and 14B. BP4_Strong BP6_Moderate BS1 BS2

The NM_003680.4(YARS1):​c.*106C>T variant causes a 3 prime UTR change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.000776 in 1,076,494 control chromosomes in the GnomAD database, including 9 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Likely benign (★).

• Frequency:
  • Genomes: 𝑓 0.0035 (7 hom., cov: 32)
  • Exomes 𝑓: 0.00033 (2 hom.)
• Consequence: YARS1 NM_003680.4 3_prime_UTR
• Clinical Significance: Likely benign criteria provided, single submitter B:1
• Conservation: PhyloP100: 0.103
• Publications: 1 publications found

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]

YARS1 Gene-Disease associations (from GenCC):

• Charcot-Marie-Tooth disease

  Inheritance: AD Classification: DEFINITIVE Submitted by: ClinGen
• Charcot-Marie-Tooth disease dominant intermediate C

  Inheritance: AD Classification: STRONG, SUPPORTIVE Submitted by: Labcorp Genetics (formerly Invitae), Orphanet
• neurologic, endocrine, and pancreatic disease, multisystem, infantile-onset 2

  Inheritance: AR Classification: STRONG Submitted by: Labcorp Genetics (formerly Invitae)

ACMG classification

Our verdict: Benign. The variant received -14 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.84).
• BP6: Variant 1-32775875-G-A is Benign according to our data. Variant chr1-32775875-G-A is described in ClinVar as Likely_benign. ClinVar VariationId is 1200883.Status of the report is criteria_provided_single_submitter, 1 stars.
• BS1: Variant frequency is greater than expected in population afr. GnomAd4 allele frequency = 0.00346 (526/152174) while in subpopulation AFR AF = 0.012 (498/41512). AF 95% confidence interval is 0.0111. There are 7 homozygotes in GnomAd4. There are 247 alleles in the male GnomAd4 subpopulation. Median coverage is 32. This position passed quality control check.
• BS2: High Homozygotes in GnomAd4 at 7 AD,AR gene

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_003680.4. You can select a different transcript below to see updated ACMG assignments.

RefSeq Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	YARS1	NM_003680.4	MANE Select	c.*106C>T		3_prime_UTR	Exon 13 of 13	NP_003671.1	P54577

Ensembl Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	YARS1	ENST00000373477.9	TSL:1 MANE Select	c.*106C>T		3_prime_UTR	Exon 13 of 13	ENSP00000362576.4	P54577
	YARS1	ENST00000906066.1		c.*106C>T		3_prime_UTR	Exon 14 of 14	ENSP00000576125.1
	YARS1	ENST00000918766.1		c.*106C>T		3_prime_UTR	Exon 13 of 13	ENSP00000588825.1

Frequencies

GnomAD3 genomes AF: 0.00337 AC: 512 AN: 152056 Hom.: 5 Cov.: 32

Gnomad AFR AF: 0.0117

Gnomad AMI AF: 0.00

Gnomad AMR AF: 0.00118

Gnomad ASJ AF: 0.00

Gnomad EAS AF: 0.00

Gnomad SAS AF: 0.000207

Gnomad FIN AF: 0.00

Gnomad MID AF: 0.00

Gnomad NFE AF: 0.0000147

Gnomad OTH AF: 0.00384

GnomAD4 exome AF: 0.000334 AC: 309 AN: 924320 Hom.: 2 Cov.: 12 AF XY: 0.000273 AC XY: 130 AN XY: 476304

African (AFR) AF: 0.0121 AC: 273 AN: 22502

American (AMR) AF: 0.000299 AC: 11 AN: 36834

Ashkenazi Jewish (ASJ) AF: 0.00 AC: 0 AN: 22174

East Asian (EAS) AF: 0.00 AC: 0 AN: 34838

South Asian (SAS) AF: 0.0000141 AC: 1 AN: 70820

European-Finnish (FIN) AF: 0.0000201 AC: 1 AN: 49848

Middle Eastern (MID) AF: 0.000312 AC: 1 AN: 3204

European-Non Finnish (NFE) AF: 0.00000468 AC: 3 AN: 641582

Other (OTH) AF: 0.000447 AC: 19 AN: 42518

GnomAD4 genome AF: 0.00346 AC: 526 AN: 152174 Hom.: 7 Cov.: 32 AF XY: 0.00332 AC XY: 247 AN XY: 74372

African (AFR) AF: 0.0120 AC: 498 AN: 41512

American (AMR) AF: 0.00118 AC: 18 AN: 15274

Ashkenazi Jewish (ASJ) AF: 0.00 AC: 0 AN: 3470

East Asian (EAS) AF: 0.00 AC: 0 AN: 5172

South Asian (SAS) AF: 0.000208 AC: 1 AN: 4818

European-Finnish (FIN) AF: 0.00 AC: 0 AN: 10602

Middle Eastern (MID) AF: 0.00 AC: 0 AN: 292

European-Non Finnish (NFE) AF: 0.0000147 AC: 1 AN: 68016

Other (OTH) AF: 0.00380 AC: 8 AN: 2106

Alfa AF: 0.00326 Hom.: 0

Bravo AF: 0.00380

Asia WGS AF: 0.000866 AC: 3 AN: 3478

ClinVar

ClinVar submissions

Significance: Likely benign

Revision: criteria provided, single submitter

Pathogenic	VUS	Benign	Condition
-	-	1	not provided (1)

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.84
CADD	Benign	11
DANN	Benign	0.71
PhyloP100		0.10
RBP_binding_hub_radar		0.0
RBP_regulation_power_radar		1.3
Mutation Taster		=100/0	polymorphism

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

Other links and lift over

dbSNP: rs112037794; hg19: chr1-33241476;