2-222656259-A-T

Variant names:

• chr2-222656259-A-T
• rs2044537
• NM_005687.5:c.-186T>A

Variant summary

Our verdict is Likely benign. Variant got -6 ACMG points: 2P and 8B. PM2 BP4_Strong BS1

The NM_005687.5(FARSB):​c.-186T>A variant causes a upstream gene change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00061 in 578,376 control chromosomes in the GnomAD database, with no homozygous occurrence. 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 0.00051 (0 hom., cov: 36)
  • Exomes 𝑓: 0.00065 (0 hom.)
• Consequence: FARSB NM_005687.5 upstream_gene
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -2.77

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]

LOC124907985 (HGNC:):

ACMG classification

Verdict is Likely_benign. Variant got -6 ACMG points.

• PM2: Very rare variant in population databases, with high coverage
• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.82).
• BS1: Variant frequency is greater than expected in population nfe. gnomad4 allele frequency = 0.000506 (77/152214) while in subpopulation NFE AF= 0.000882 (60/68028). AF 95% confidence interval is 0.000703. There are 0 homozygotes in gnomad4. There are 27 alleles in male gnomad4 subpopulation. Median coverage is 36. This position pass quality control queck.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
FARSB	NM_005687.5	c.-186T>A		upstream_gene_variant		ENST00000281828.8	NP_005678.3

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
FARSB	ENST00000281828.8	c.-186T>A		upstream_gene_variant		1	NM_005687.5	ENSP00000281828.6

Frequencies

GnomAD3 genomes AF: 0.000506 AC: 77 AN: 152214 Hom.: 0 Cov.: 36

Gnomad AFR AF: 0.000289

Gnomad AMI AF: 0.00

Gnomad AMR AF: 0.000262

Gnomad ASJ AF: 0.00

Gnomad EAS AF: 0.000193

Gnomad SAS AF: 0.00

Gnomad FIN AF: 0.00

Gnomad MID AF: 0.00

Gnomad NFE AF: 0.000882

Gnomad OTH AF: 0.00

GnomAD4 exome AF: 0.000648 AC: 276 AN: 426162 Hom.: 0 Cov.: 3 AF XY: 0.000658 AC XY: 148 AN XY: 224814

Gnomad4 AFR exome AF: 0.000204

Gnomad4 AMR exome AF: 0.000435

Gnomad4 ASJ exome AF: 0.00

Gnomad4 EAS exome AF: 0.000377

Gnomad4 SAS exome AF: 0.0000471

Gnomad4 FIN exome AF: 0.00

Gnomad4 NFE exome AF: 0.000883

Gnomad4 OTH exome AF: 0.00112

GnomAD4 genome AF: 0.000506 AC: 77 AN: 152214 Hom.: 0 Cov.: 36 AF XY: 0.000363 AC XY: 27 AN XY: 74370

Gnomad4 AFR AF: 0.000289

Gnomad4 AMR AF: 0.000262

Gnomad4 ASJ AF: 0.00

Gnomad4 EAS AF: 0.000193

Gnomad4 SAS AF: 0.00

Gnomad4 FIN AF: 0.00

Gnomad4 NFE AF: 0.000882

Gnomad4 OTH AF: 0.00

Alfa AF: 0.0000977 Hom.: 3538

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.82
CADD	Benign	0.0020
DANN	Benign	0.50

Splicing

Name	Calibrated prediction	Score	Prediction
SpliceAI score (max)		0.010		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: rs2044537; hg19: chr2-223520978;