chr2-222567378-T-C

Position:

• chr2-222567378-T-C

Variant summary

Our verdict is Benign. Variant got -12 ACMG points: 0P and 12B. BP4_Strong BA1

The NM_005687.5(FARSB):​c.*4493A>G variant causes a 3 prime UTR change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.311 in 152,196 control chromosomes in the GnomAD database, including 7,580 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 0.31 (7580 hom., cov: 33)
  • Exomes 𝑓: 0.10 (0 hom.)
• Consequence: FARSB NM_005687.5 3_prime_UTR
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 0.0520

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 -12 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.94).
• BA1: GnomAd4 highest subpopulation (SAS) allele frequency at 95% confidence interval = 0.418 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
FARSB	NM_005687.5	c.*4493A>G		3_prime_UTR_variant	17/17	ENST00000281828.8
FARSB	XM_006712169.3	c.*4493A>G		3_prime_UTR_variant	18/18
FARSB	XM_011510466.3	c.*4493A>G		3_prime_UTR_variant	18/18
FARSB	NR_130154.2	n.6478A>G		non_coding_transcript_exon_variant	18/18

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
FARSB	ENST00000281828.8	c.*4493A>G		3_prime_UTR_variant	17/17	1	NM_005687.5	P1
FARSB	ENST00000568928.3	n.723A>G		non_coding_transcript_exon_variant	2/2

Frequencies

GnomAD3 genomes AF: 0.311 AC: 47268 AN: 152068 Hom.: 7581 Cov.: 33

Gnomad AFR AF: 0.278

Gnomad AMI AF: 0.302

Gnomad AMR AF: 0.310

Gnomad ASJ AF: 0.450

Gnomad EAS AF: 0.124

Gnomad SAS AF: 0.433

Gnomad FIN AF: 0.279

Gnomad MID AF: 0.456

Gnomad NFE AF: 0.333

Gnomad OTH AF: 0.344

GnomAD4 exome AF: 0.100 AC: 1 AN: 10 Hom.: 0 Cov.: 0 AF XY: 0.125 AC XY: 1 AN XY: 8

Gnomad4 AFR exome AF: 0.00

Gnomad4 NFE exome AF: 0.125

GnomAD4 genome AF: 0.311 AC: 47277 AN: 152186 Hom.: 7580 Cov.: 33 AF XY: 0.309 AC XY: 22960 AN XY: 74392

Gnomad4 AFR AF: 0.277

Gnomad4 AMR AF: 0.310

Gnomad4 ASJ AF: 0.450

Gnomad4 EAS AF: 0.124

Gnomad4 SAS AF: 0.434

Gnomad4 FIN AF: 0.279

Gnomad4 NFE AF: 0.333

Gnomad4 OTH AF: 0.339

Alfa AF: 0.268 Hom.: 1279

Bravo AF: 0.310

Asia WGS AF: 0.273 AC: 953 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.94
CADD	Benign	4.5
DANN	Benign	0.77

Splicing

Find out detailed SpliceAI scores and Pangolin per-transcript scores at spliceailookup.broadinstitute.org

Publications

LitVar

Other links and lift over

dbSNP: rs16863886; hg19: chr2-223432097;