2-222571867-A-G

Variant summary

Our verdict is Benign. Variant got -14 ACMG points: 0P and 14B. BP4_Strong BP6_Moderate BS1 BS2

The NM_005687.5(FARSB):c.*4T>C variant causes a 3 prime UTR change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0202 in 1,611,296 control chromosomes in the GnomAD database, including 392 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★).

• Frequency:
  • Genomes: 𝑓 0.016 (21 hom., cov: 32)
  • Exomes 𝑓: 0.021 (371 hom.)
• Consequence: FARSB NM_005687.5 3_prime_UTR
• Clinical Significance: Benign criteria provided, single submitter B:1
• Conservation: PhyloP100: -0.209

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]

ACMG classification

Verdict is Benign. Variant got -14 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.53).
• BP6: Variant 2-222571867-A-G is Benign according to our data. Variant chr2-222571867-A-G is described in ClinVar as [Benign]. Clinvar id is 3056152.Status of the report is criteria_provided_single_submitter, 1 stars.
• BS1: Variant frequency is greater than expected in population amr. gnomad4 allele frequency = 0.0158 (2398/152226) while in subpopulation AMR AF= 0.0229 (350/15296). AF 95% confidence interval is 0.0217. There are 21 homozygotes in gnomad4. There are 1150 alleles in male gnomad4 subpopulation. Median coverage is 32. This position pass quality control queck.
• BS2: High Homozygotes in GnomAd at 21 AR gene

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
FARSB	NM_005687.5	c.*4T>C		3_prime_UTR_variant	17/17	ENST00000281828.8
FARSB	XM_006712169.3	c.*4T>C		3_prime_UTR_variant	18/18
FARSB	XM_011510466.3	c.*4T>C		3_prime_UTR_variant	18/18
FARSB	NR_130154.2	n.1989T>C		non_coding_transcript_exon_variant	18/18

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
FARSB	ENST00000281828.8	c.*4T>C		3_prime_UTR_variant	17/17	1	NM_005687.5	P1

Frequencies

GnomAD3 genomes AF: 0.0158 AC: 2401 AN: 152108 Hom.: 21 Cov.: 32

Gnomad AFR AF: 0.00444

Gnomad AMI AF: 0.00

Gnomad AMR AF: 0.0229

Gnomad ASJ AF: 0.0323

Gnomad EAS AF: 0.00

Gnomad SAS AF: 0.000832

Gnomad FIN AF: 0.0156

Gnomad MID AF: 0.0190

Gnomad NFE AF: 0.0227

Gnomad OTH AF: 0.0177

GnomAD3 exomes AF: 0.0149 AC: 3693 AN: 248500 Hom.: 40 AF XY: 0.0149 AC XY: 1994 AN XY: 134218

Gnomad AFR exome AF: 0.00385

Gnomad AMR exome AF: 0.0129

Gnomad ASJ exome AF: 0.0293

Gnomad EAS exome AF: 0.00

Gnomad SAS exome AF: 0.00130

Gnomad FIN exome AF: 0.0146

Gnomad NFE exome AF: 0.0218

Gnomad OTH exome AF: 0.0157

GnomAD4 exome AF: 0.0206 AC: 30077 AN: 1459070 Hom.: 371 Cov.: 28 AF XY: 0.0202 AC XY: 14638 AN XY: 725838

Gnomad4 AFR exome AF: 0.00342

Gnomad4 AMR exome AF: 0.0132

Gnomad4 ASJ exome AF: 0.0304

Gnomad4 EAS exome AF: 0.0000252

Gnomad4 SAS exome AF: 0.00125

Gnomad4 FIN exome AF: 0.0139

Gnomad4 NFE exome AF: 0.0239

Gnomad4 OTH exome AF: 0.0198

GnomAD4 genome AF: 0.0158 AC: 2398 AN: 152226 Hom.: 21 Cov.: 32 AF XY: 0.0155 AC XY: 1150 AN XY: 74420

Gnomad4 AFR AF: 0.00443

Gnomad4 AMR AF: 0.0229

Gnomad4 ASJ AF: 0.0323

Gnomad4 EAS AF: 0.00

Gnomad4 SAS AF: 0.000832

Gnomad4 FIN AF: 0.0156

Gnomad4 NFE AF: 0.0227

Gnomad4 OTH AF: 0.0175

Alfa AF: 0.0203 Hom.: 13

Bravo AF: 0.0156

ClinVar

Significance: Benign

Submissions summary: Benign:1

Revision: criteria provided, single submitter

Submissions by phenotype

FARSB-related disorder Benign:1

Benign, criteria provided, single submitter

clinical testing

PreventionGenetics, part of Exact Sciences

Nov 21, 2023

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: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.53
Cadd	Benign	8.6
Dann	Benign	0.78
RBP_binding_hub_radar		0.0
RBP_regulation_power_radar		1.1

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

Publications

LitVar

Other links and lift over

dbSNP: rs116655892; hg19: chr2-223436586;