chr2-222656186-G-C

Variant names:

• chr2-222656186-G-C
• rs2166652
• NM_005687.5:c.-113C>G

Variant summary

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

The NM_005687.5(FARSB):​c.-113C>G variant causes a upstream gene change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.822 in 712,212 control chromosomes in the GnomAD database, including 244,716 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 0.85 (56406 hom., cov: 36)
  • Exomes 𝑓: 0.81 (188310 hom.)
• Consequence: FARSB NM_005687.5 upstream_gene
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.0860
• Publications: 4 publications found

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]

FARSB Gene-Disease associations (from GenCC):

• Rajab interstitial lung disease with brain calcifications 1

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

LOC124907985 (HGNC:):

ACMG classification

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

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.8).
• BA1: GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.958 is higher than 0.05.

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_005687.5. You can select a different transcript below to see updated ACMG assignments.

RefSeq Transcripts

Selected	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	FARSB	NM_005687.5	MANE Select	c.-113C>G		upstream_gene	N/A	NP_005678.3
	FARSB	NR_130154.2		n.-94C>G		upstream_gene	N/A

Ensembl Transcripts

Selected	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	FARSB	ENST00000281828.8	TSL:1 MANE Select	c.-113C>G		upstream_gene	N/A	ENSP00000281828.6

Frequencies

GnomAD3 genomes AF: 0.854 AC: 129948 AN: 152244 Hom.: 56360 Cov.: 36

Gnomad AFR AF: 0.966

Gnomad AMI AF: 0.878

Gnomad AMR AF: 0.764

Gnomad ASJ AF: 0.863

Gnomad EAS AF: 0.440

Gnomad SAS AF: 0.782

Gnomad FIN AF: 0.787

Gnomad MID AF: 0.949

Gnomad NFE AF: 0.851

Gnomad OTH AF: 0.862

GnomAD4 exome AF: 0.813 AC: 455072 AN: 559850 Hom.: 188310 Cov.: 7 AF XY: 0.813 AC XY: 241402 AN XY: 296974

African (AFR) AF: 0.964 AC: 11773 AN: 12214

American (AMR) AF: 0.727 AC: 13064 AN: 17960

Ashkenazi Jewish (ASJ) AF: 0.864 AC: 15345 AN: 17754

East Asian (EAS) AF: 0.406 AC: 11751 AN: 28922

South Asian (SAS) AF: 0.797 AC: 43938 AN: 55160

European-Finnish (FIN) AF: 0.780 AC: 36791 AN: 47142

Middle Eastern (MID) AF: 0.911 AC: 3596 AN: 3946

European-Non Finnish (NFE) AF: 0.848 AC: 294412 AN: 347180

Other (OTH) AF: 0.825 AC: 24402 AN: 29572

GnomAD4 genome AF: 0.853 AC: 130040 AN: 152362 Hom.: 56406 Cov.: 36 AF XY: 0.844 AC XY: 62909 AN XY: 74502

African (AFR) AF: 0.966 AC: 40175 AN: 41602

American (AMR) AF: 0.762 AC: 11669 AN: 15308

Ashkenazi Jewish (ASJ) AF: 0.863 AC: 2996 AN: 3472

East Asian (EAS) AF: 0.440 AC: 2280 AN: 5178

South Asian (SAS) AF: 0.783 AC: 3782 AN: 4832

European-Finnish (FIN) AF: 0.787 AC: 8355 AN: 10620

Middle Eastern (MID) AF: 0.952 AC: 280 AN: 294

European-Non Finnish (NFE) AF: 0.851 AC: 57890 AN: 68030

Other (OTH) AF: 0.857 AC: 1812 AN: 2114

Alfa AF: 0.788 Hom.: 2377

Bravo AF: 0.856

Asia WGS AF: 0.642 AC: 2234 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.80
CADD	Benign	6.0
DANN	Benign	0.65
PhyloP100		-0.086
PromoterAI		0.047	Neutral
Mutation Taster		=300/0	polymorphism (auto)

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: rs2166652; hg19: chr2-223520905; COSMIC: COSV56052419;