rs2293683

Variant names:

• chr19-12928470-A-G
• rs2293683
• ENST00000592662.5:n.792T>C

Your query was ambiguous. Multiple possible variants found:

• chr19-12928470-A-G
• chr19-12928470-A-T

Variant summary

Our verdict is Benign. The variant received -12 ACMG points: 0P and 12B. BP4_Strong BA1

The ENST00000592662.5(FARSA):​n.792T>C variant causes a non coding transcript exon change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.646 in 1,613,602 control chromosomes in the GnomAD database, including 339,392 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 0.64 (31673 hom., cov: 31)
  • Exomes 𝑓: 0.65 (307719 hom.)
• Consequence: FARSA ENST00000592662.5 non_coding_transcript_exon
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -1.33
• Publications: 31 publications found

Genes affected

FARSA (HGNC:3592): (phenylalanyl-tRNA synthetase subunit alpha) Aminoacyl-tRNA synthetases are a class of enzymes that charge tRNAs with their cognate amino acids. This gene encodes a product which is similar to the catalytic subunit of prokaryotic and Saccharomyces cerevisiae phenylalanyl-tRNA synthetases (PheRS). This gene product has been shown to be expressed in a tumor-selective and cell cycle stage- and differentiation-dependent manner, the first member of the tRNA synthetase gene family shown to exhibit this type of regulated expression [provided by RefSeq, Jul 2008]

FARSA Gene-Disease associations (from GenCC):

• Rajab interstitial lung disease with brain calcifications 2

  Inheritance: AR Classification: STRONG, LIMITED Submitted by: Ambry Genetics, Labcorp Genetics (formerly Invitae), PanelApp Australia

ACMG classification

Our verdict: Benign. The variant received -12 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.89).
• BA1: GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.797 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
FARSA	NM_004461.3	c.726-13T>C		intron_variant	Intron 6 of 12	ENST00000314606.9	NP_004452.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
FARSA	ENST00000314606.9	c.726-13T>C		intron_variant	Intron 6 of 12	1	NM_004461.3	ENSP00000320309.3

Frequencies

GnomAD3 genomes AF: 0.643 AC: 97573 AN: 151844 Hom.: 31646 Cov.: 31

Gnomad AFR AF: 0.612

Gnomad AMI AF: 0.615

Gnomad AMR AF: 0.591

Gnomad ASJ AF: 0.724

Gnomad EAS AF: 0.818

Gnomad SAS AF: 0.726

Gnomad FIN AF: 0.706

Gnomad MID AF: 0.699

Gnomad NFE AF: 0.639

Gnomad OTH AF: 0.643

GnomAD2 exomes AF: 0.654 AC: 164302 AN: 251044 AF XY: 0.661

Gnomad AFR exome AF: 0.611

Gnomad AMR exome AF: 0.524

Gnomad ASJ exome AF: 0.724

Gnomad EAS exome AF: 0.820

Gnomad FIN exome AF: 0.703

Gnomad NFE exome AF: 0.639

Gnomad OTH exome AF: 0.659

GnomAD4 exome AF: 0.646 AC: 944432 AN: 1461640 Hom.: 307719 Cov.: 51 AF XY: 0.650 AC XY: 472570 AN XY: 727112

African (AFR) AF: 0.619 AC: 20727 AN: 33480

American (AMR) AF: 0.532 AC: 23781 AN: 44712

Ashkenazi Jewish (ASJ) AF: 0.727 AC: 18976 AN: 26118

East Asian (EAS) AF: 0.839 AC: 33293 AN: 39696

South Asian (SAS) AF: 0.720 AC: 62094 AN: 86250

European-Finnish (FIN) AF: 0.697 AC: 37178 AN: 53360

Middle Eastern (MID) AF: 0.693 AC: 3996 AN: 5768

European-Non Finnish (NFE) AF: 0.634 AC: 704601 AN: 1111870

Other (OTH) AF: 0.659 AC: 39786 AN: 60386

GnomAD4 genome AF: 0.643 AC: 97641 AN: 151962 Hom.: 31673 Cov.: 31 AF XY: 0.647 AC XY: 47996 AN XY: 74234

African (AFR) AF: 0.613 AC: 25408 AN: 41444

American (AMR) AF: 0.590 AC: 8995 AN: 15256

Ashkenazi Jewish (ASJ) AF: 0.724 AC: 2514 AN: 3470

East Asian (EAS) AF: 0.818 AC: 4212 AN: 5150

South Asian (SAS) AF: 0.726 AC: 3495 AN: 4814

European-Finnish (FIN) AF: 0.706 AC: 7466 AN: 10576

Middle Eastern (MID) AF: 0.704 AC: 207 AN: 294

European-Non Finnish (NFE) AF: 0.639 AC: 43438 AN: 67940

Other (OTH) AF: 0.639 AC: 1348 AN: 2110

Alfa AF: 0.642 Hom.: 105005

Bravo AF: 0.630

Asia WGS AF: 0.727 AC: 2527 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.89
CADD	Benign	0.067
DANN	Benign	0.35
PhyloP100		-1.3
BranchPoint Hunter		1.0
PromoterAI		0.022	Neutral
RBP_binding_hub_radar		0.0
RBP_regulation_power_radar		1.0
Mutation Taster		=100/0	polymorphism (auto)

Splicing

Name	Calibrated prediction	Score	Prediction
SpliceAI score (max)		0.030		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: rs2293683; hg19: chr19-13039284;