Genetic Variant NM_005687.5:c.-113C>G (chr2-222656186-G-C) – 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.-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

Scores

Clinical Significance

Not reported in ClinVar

Conservation

PhyloP100: -0.0860

Publications

4 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:

LOC124907985 (HGNC:):

LOC124907985 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=-0.8).

BA1

GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.958 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
FARSB	NM_005687.5 link	c.-113C>G		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.-113C>G		upstream_gene_variant		1	NM_005687.5	ENSP00000281828.6		Q9NSD9-1

Frequencies

GnomAD3 genomes

AF:

0.854

AC:

129948

AN:

152244

Hom.:

56360

Cov.:

show subpopulations

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.:

AF XY:

0.813

AC XY:

241402

AN XY:

296974

show subpopulations

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

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.500

Heterozygous variant carriers

4095

8190

12284

16379

20474

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Exome Het

Exome Hom

Variant carriers

2308

4616

6924

9232

11540

<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:

130040

AN:

152362

Hom.:

56406

Cov.:

AF XY:

0.844

AC XY:

62909

AN XY:

74502

show subpopulations

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

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.507

Heterozygous variant carriers

932

1865

2797

3730

4662

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Genome Het

Genome Hom

Variant carriers

882

1764

2646

3528

4410

<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:

0.788

Hom.:

2377

Bravo

AF:

0.856

Asia WGS

AF:

0.642

AC:

2234

AN:

3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

BayesDel_noAF

Benign

-0.80

CADD

Benign

6.0

(source)

DANN

Benign

0.65

PhyloP100

-0.086

PromoterAI

0.047

Neutral

(source)

Mutation Taster

=300/0

polymorphism (auto)

(source)

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

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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