chr2-222572000-T-G
Variant summary
Our verdict is Benign. Variant got -15 ACMG points: 0P and 15B. BP4_ModerateBP6_Very_StrongBP7BS1
The NM_005687.5(FARSB):c.1641A>C(p.Arg547=) variant causes a synonymous change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.000524 in 1,613,422 control chromosomes in the GnomAD database, including 14 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Likely benign (★★).
Frequency
Genomes: 𝑓 0.00058 ( 1 hom., cov: 31)
Exomes 𝑓: 0.00052 ( 13 hom. )
Consequence
FARSB
NM_005687.5 synonymous
NM_005687.5 synonymous
Scores
2
Clinical Significance
Conservation
PhyloP100: 0.229
Genes affected
FARSB (HGNC:17800): (phenylalanyl-tRNA synthetase subunit beta) This gene encodes a highly conserved enzyme that belongs to the aminoacyl-tRNA synthetase class IIc subfamily. This enzyme comprises the regulatory beta subunits that form a tetramer with two catalytic alpha subunits. In the presence of ATP, this tetramer is responsible for attaching L-phenylalanine to the terminal adenosine of the appropriate tRNA. A pseudogene located on chromosome 10 has been identified. Alternative splicing results in multiple transcript variants. [provided by RefSeq, Jan 2015]
Genome browser will be placed here
ACMG classification
Classification made for transcript
Verdict is Benign. Variant got -15 ACMG points.
BP4
?
Computational evidence support a benign effect (BayesDel_noAF=-0.38).
BP6
?
Variant 2-222572000-T-G is Benign according to our data. Variant chr2-222572000-T-G is described in ClinVar as [Likely_benign]. Clinvar id is 1599295.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars.
BP7
?
Synonymous conserved (PhyloP=0.229 with no splicing effect.
BS1
?
Variant frequency is greater than expected in population eas. gnomad4 allele frequency = 0.000585 (89/152152) while in subpopulation EAS AF= 0.0154 (80/5190). AF 95% confidence interval is 0.0127. There are 1 homozygotes in gnomad4. There are 38 alleles in male gnomad4 subpopulation. Median coverage is 31. This position pass quality control queck.
Transcripts
RefSeq
Gene | Transcript | HGVSc | HGVSp | Effect | #exon/exons | MANE | UniProt |
---|---|---|---|---|---|---|---|
FARSB | NM_005687.5 | c.1641A>C | p.Arg547= | synonymous_variant | 17/17 | ENST00000281828.8 | |
FARSB | XM_006712169.3 | c.1344A>C | p.Arg448= | synonymous_variant | 18/18 | ||
FARSB | XM_011510466.3 | c.1344A>C | p.Arg448= | synonymous_variant | 18/18 | ||
FARSB | NR_130154.2 | n.1856A>C | non_coding_transcript_exon_variant | 18/18 |
Ensembl
Gene | Transcript | HGVSc | HGVSp | Effect | #exon/exons | TSL | MANE | Appris | UniProt |
---|---|---|---|---|---|---|---|---|---|
FARSB | ENST00000281828.8 | c.1641A>C | p.Arg547= | synonymous_variant | 17/17 | 1 | NM_005687.5 | P1 |
Frequencies
GnomAD3 genomes ? AF: 0.000585 AC: 89AN: 152034Hom.: 1 Cov.: 31
GnomAD3 genomes
?
AF:
AC:
89
AN:
152034
Hom.:
Cov.:
31
Gnomad AFR
AF:
Gnomad AMI
AF:
Gnomad AMR
AF:
Gnomad ASJ
AF:
Gnomad EAS
AF:
Gnomad SAS
AF:
Gnomad FIN
AF:
Gnomad MID
AF:
Gnomad NFE
AF:
Gnomad OTH
AF:
GnomAD3 exomes AF: 0.000825 AC: 206AN: 249744Hom.: 1 AF XY: 0.000777 AC XY: 105AN XY: 135098
GnomAD3 exomes
AF:
AC:
206
AN:
249744
Hom.:
AF XY:
AC XY:
105
AN XY:
135098
Gnomad AFR exome
AF:
Gnomad AMR exome
AF:
Gnomad ASJ exome
AF:
Gnomad EAS exome
AF:
Gnomad SAS exome
AF:
Gnomad FIN exome
AF:
Gnomad NFE exome
AF:
Gnomad OTH exome
AF:
GnomAD4 exome AF: 0.000517 AC: 756AN: 1461270Hom.: 13 Cov.: 33 AF XY: 0.000524 AC XY: 381AN XY: 726968
GnomAD4 exome
AF:
AC:
756
AN:
1461270
Hom.:
Cov.:
33
AF XY:
AC XY:
381
AN XY:
726968
Gnomad4 AFR exome
AF:
Gnomad4 AMR exome
AF:
Gnomad4 ASJ exome
AF:
Gnomad4 EAS exome
AF:
Gnomad4 SAS exome
AF:
Gnomad4 FIN exome
AF:
Gnomad4 NFE exome
AF:
Gnomad4 OTH exome
AF:
GnomAD4 genome ? AF: 0.000585 AC: 89AN: 152152Hom.: 1 Cov.: 31 AF XY: 0.000511 AC XY: 38AN XY: 74392
GnomAD4 genome
?
AF:
AC:
89
AN:
152152
Hom.:
Cov.:
31
AF XY:
AC XY:
38
AN XY:
74392
Gnomad4 AFR
AF:
Gnomad4 AMR
AF:
Gnomad4 ASJ
AF:
Gnomad4 EAS
AF:
Gnomad4 SAS
AF:
Gnomad4 FIN
AF:
Gnomad4 NFE
AF:
Gnomad4 OTH
AF:
Alfa
AF:
Hom.:
Bravo
AF:
Asia WGS
AF:
AC:
14
AN:
3478
ClinVar
Significance: Benign/Likely benign
Submissions summary: Benign:3
Revision: criteria provided, multiple submitters, no conflicts
LINK: link
Submissions by phenotype
not provided Benign:2
Likely benign, criteria provided, single submitter | clinical testing | CeGaT Center for Human Genetics Tuebingen | Feb 01, 2023 | FARSB: BP4, BP7, BS1 - |
Benign, criteria provided, single submitter | clinical testing | Invitae | Oct 27, 2023 | - - |
FARSB-related disorder Benign:1
Benign, criteria provided, single submitter | clinical testing | PreventionGenetics, part of Exact Sciences | May 22, 2019 | This variant is classified as benign based on ACMG/AMP sequence variant interpretation guidelines (Richards et al. 2015 PMID: 25741868, with internal and published modifications). - |
Computational scores
Source:
Name
Calibrated prediction
Score
Prediction
BayesDel_noAF
Benign
Cadd
Benign
Dann
Benign
Splicing
Name
Calibrated prediction
Score
Prediction
SpliceAI score (max)
Details are displayed if max score is > 0.2
Find out detailed SpliceAI scores and Pangolin per-transcript scores at