Genetic Variant FARSB:c.-186T>C (chr2-222656259-A-G) – ACMG Classification: Benign (-12 pts)

Variant summary

Our verdict is Benign. The variant received -12 ACMG points: 0P and 12B. BP4_StrongBA1

The NM_005687.5(FARSB):c.-186T>C variant causes a upstream gene change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.821 in 578,190 control chromosomes in the GnomAD database, including 198,579 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 ( 56330 hom., cov: 36)

Exomes 𝑓: 0.81 ( 142249 hom. )

Consequence

FARSB
NM_005687.5 upstream_gene

Scores

Clinical Significance

Not reported in ClinVar

Conservation

PhyloP100: -2.77

Publications

5 publications found

Variant links:

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

FARSB links:

ENSG00000303347 (HGNC:):

ENSG00000303347 links:

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ACMG classification

Classification was made for transcript

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

BP4

Computational evidence support a benign effect (BayesDel_noAF=-0.81).

BA1

GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.959 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
FARSB	NM_005687.5 link	c.-186T>C		upstream_gene_variant		ENST00000281828.8	NP_005678.3	Q9NSD9-1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
FARSB	ENST00000281828.8 link	c.-186T>C		upstream_gene_variant		1	NM_005687.5	ENSP00000281828.6		Q9NSD9-1
ENSG00000303347	ENST00000793840.1 link	n.-179A>G		upstream_gene_variant

Frequencies

GnomAD3 genomes

AF:

0.853

AC:

129831

AN:

152198

Hom.:

56284

Cov.:

show subpopulations

Gnomad AFR

AF:

0.967

Gnomad AMI

AF:

0.878

Gnomad AMR

AF:

0.763

Gnomad ASJ

AF:

0.859

Gnomad EAS

AF:

0.440

Gnomad SAS

AF:

0.776

Gnomad FIN

AF:

0.786

Gnomad MID

AF:

0.949

Gnomad NFE

AF:

0.850

Gnomad OTH

AF:

0.861

GnomAD4 exome

AF:

0.809

AC:

344593

AN:

425874

Hom.:

142249

Cov.:

AF XY:

0.809

AC XY:

181855

AN XY:

224674

show subpopulations

African (AFR)

AF:

0.963

AC:

9449

AN:

9808

American (AMR)

AF:

0.735

AC:

10118

AN:

13768

Ashkenazi Jewish (ASJ)

AF:

0.864

AC:

11755

AN:

13608

East Asian (EAS)

AF:

0.408

AC:

10814

AN:

26488

South Asian (SAS)

AF:

0.793

AC:

33616

AN:

42398

European-Finnish (FIN)

AF:

0.784

AC:

26288

AN:

33538

Middle Eastern (MID)

AF:

0.915

AC:

3020

AN:

3302

European-Non Finnish (NFE)

AF:

0.849

AC:

219022

AN:

258088

Other (OTH)

AF:

0.825

AC:

20511

AN:

24876

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.503

Heterozygous variant carriers

2998

5995

8993

11990

14988

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Exome Het

Exome Hom

Variant carriers

732

1464

2196

2928

3660

<30

30-35

35-40

40-45

45-50

50-55

55-60

60-65

65-70

70-75

75-80

>80

Age

GnomAD4 genome

AF:

0.853

AC:

129923

AN:

152316

Hom.:

56330

Cov.:

AF XY:

0.844

AC XY:

62866

AN XY:

74488

show subpopulations

African (AFR)

AF:

0.967

AC:

40196

AN:

41588

American (AMR)

AF:

0.762

AC:

11659

AN:

15298

Ashkenazi Jewish (ASJ)

AF:

0.859

AC:

2981

AN:

3470

East Asian (EAS)

AF:

0.440

AC:

2278

AN:

5174

South Asian (SAS)

AF:

0.777

AC:

3754

AN:

4830

European-Finnish (FIN)

AF:

0.786

AC:

8348

AN:

10618

Middle Eastern (MID)

AF:

0.952

AC:

280

AN:

294

European-Non Finnish (NFE)

AF:

0.850

AC:

57814

AN:

68016

Other (OTH)

AF:

0.856

AC:

1812

AN:

2116

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.509

Heterozygous variant carriers

955

1910

2866

3821

4776

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Genome Het

Genome Hom

Variant carriers

880

1760

2640

3520

4400

<30

30-35

35-40

40-45

45-50

50-55

55-60

60-65

65-70

70-75

75-80

>80

Age

Alfa

AF:

0.817

Hom.:

3538

Bravo

AF:

0.856

Asia WGS

AF:

0.640

AC:

2227

AN:

3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

BayesDel_noAF

Benign

-0.81

CADD

Benign

0.0030

(source)

DANN

Benign

0.52

PhyloP100

-2.8

PromoterAI

0.045

Neutral

(source)

Mutation Taster

=300/0

polymorphism (auto)

(source)

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

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Variant summary

Frequency

Consequence

Scores

Clinical Significance

Conservation

Publications

ACMG classification

Transcripts

RefSeq

Ensembl

Frequencies

Age Distribution

Age Distribution

ClinVar

Computational scores

Splicing

Publications

Other links and lift over