Genetic Variant FCRLB:p.Ser74Arg (chr1-161723536-C-A) – ACMG Classification: Likely_benign (-1 pts)

Variant summary

Our verdict is Likely benign. The variant received -1 ACMG points: 0P and 1B. BP4

The NM_001002901.4(FCRLB):c.222C>A(p.Ser74Arg) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0000465 in 1,614,204 control chromosomes in the GnomAD database, including 1 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Uncertain significance (★).

Frequency

Genomes: 𝑓 0.00025 ( 1 hom., cov: 32)

Exomes 𝑓: 0.000025 ( 0 hom. )

Consequence

FCRLB
NM_001002901.4 missense

Scores

Clinical Significance

Uncertain significance criteria provided, single submitter U:1

Conservation

PhyloP100: 1.41

Publications

0 publications found

Variant links:

Genes affected

FCRLB (HGNC:26431): (Fc receptor like B) FCRL2 belongs to the Fc receptor family. Fc receptors are involved in phagocytosis, antibody-dependent cell cytotoxicity, immediate hypersensitivity, and transcytosis of immunoglobulins via their ability to bind immunoglobulin (Ig) constant regions (Chikaev et al., 2005 [PubMed 15676285]).[supplied by OMIM, Mar 2008]

FCRLB links:

Genome browser will be placed here

ACMG classification

Classification was made for transcript

Our verdict: Likely_benign. The variant received -1 ACMG points.

BP4

Computational evidence support a benign effect (MetaRNN=0.31405532).

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_001002901.4. You can select a different transcript below to see updated ACMG assignments.

RefSeq Transcripts

Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
FCRLB	NM_001002901.4	MANE Select	c.222C>A	p.Ser74Arg	missense	Exon 5 of 8	NP_001002901.1	Q6BAA4-1
FCRLB	NM_001320241.1		c.222C>A	p.Ser74Arg	missense	Exon 4 of 7	NP_001307170.1	Q6BAA4-1
FCRLB	NM_001288829.1		c.222C>A	p.Ser74Arg	missense	Exon 3 of 6	NP_001275758.1	Q6BAA4-4

Ensembl Transcripts

Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
FCRLB	ENST00000367948.7	TSL:1 MANE Select	c.222C>A	p.Ser74Arg	missense	Exon 5 of 8	ENSP00000356925.2	Q6BAA4-1
FCRLB	ENST00000367946.7	TSL:1	c.222C>A	p.Ser74Arg	missense	Exon 3 of 6	ENSP00000356923.3	Q6BAA4-4
FCRLB	ENST00000367945.5	TSL:1	c.201C>A	p.Ser67Arg	missense	Exon 2 of 5	ENSP00000356922.1	Q6BAA4-5

Frequencies

GnomAD3 genomes

AF:

0.000230

AC:

AN:

152208

Hom.:

Cov.:

show subpopulations

Gnomad AFR

AF:

0.000845

Gnomad AMI

AF:

0.00

Gnomad AMR

AF:

0.00

Gnomad ASJ

AF:

0.00

Gnomad EAS

AF:

0.00

Gnomad SAS

AF:

0.00

Gnomad FIN

AF:

0.00

Gnomad MID

AF:

0.00

Gnomad NFE

AF:

0.00

Gnomad OTH

AF:

0.00

GnomAD2 exomes

AF:

0.0000557

AC:

AN:

251488

AF XY:

0.0000441

show subpopulations

Gnomad AFR exome

AF:

0.000861

Gnomad AMR exome

AF:

0.00

Gnomad ASJ exome

AF:

0.00

Gnomad EAS exome

AF:

0.00

Gnomad FIN exome

AF:

0.00

Gnomad NFE exome

AF:

0.00

Gnomad OTH exome

AF:

0.00

GnomAD4 exome

AF:

0.0000253

AC:

AN:

1461878

Hom.:

Cov.:

AF XY:

0.0000206

AC XY:

AN XY:

727244

show subpopulations

African (AFR)

AF:

0.000836

AC:

AN:

33480

American (AMR)

AF:

0.00

AC:

AN:

44724

Ashkenazi Jewish (ASJ)

AF:

0.00

AC:

AN:

26136

East Asian (EAS)

AF:

0.00

AC:

AN:

39700

South Asian (SAS)

AF:

0.00

AC:

AN:

86258

European-Finnish (FIN)

AF:

0.00

AC:

AN:

53420

Middle Eastern (MID)

AF:

0.00

AC:

AN:

5768

European-Non Finnish (NFE)

AF:

0.00000450

AC:

AN:

1111998

Other (OTH)

AF:

0.0000662

AC:

AN:

60394

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.475

Heterozygous variant carriers

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Exome Het

Variant carriers

<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:

0.000249

AC:

AN:

152326

Hom.:

Cov.:

AF XY:

0.000242

AC XY:

AN XY:

74484

show subpopulations

African (AFR)

AF:

0.000914

AC:

AN:

41554

American (AMR)

AF:

0.00

AC:

AN:

15306

Ashkenazi Jewish (ASJ)

AF:

0.00

AC:

AN:

3470

East Asian (EAS)

AF:

0.00

AC:

AN:

5186

South Asian (SAS)

AF:

0.00

AC:

AN:

4822

European-Finnish (FIN)

AF:

0.00

AC:

AN:

10632

Middle Eastern (MID)

AF:

0.00

AC:

AN:

294

European-Non Finnish (NFE)

AF:

0.00

AC:

AN:

68034

Other (OTH)

AF:

0.00

AC:

AN:

2116

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.515

Heterozygous variant carriers

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Genome Het

Variant carriers

<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:

0.000416

Hom.:

Bravo

AF:

0.000219

ESP6500AA

AF:

0.000227

AC:

ESP6500EA

AF:

0.00

AC:

ExAC

AF:

0.0000412

AC:

ClinVar

ClinVar submissions

Significance:Uncertain significance

Revision:criteria provided, single submitter

View on ClinVar

Pathogenic

VUS

Benign

Condition

not specified (1)

Computational scores

Source: dbNSFP v4.9

Name

Calibrated prediction

Score

Prediction

AlphaMissense

Uncertain

0.41

BayesDel_addAF

Benign

-0.27

BayesDel_noAF

Benign

-0.23

CADD

Benign

(source)

DANN

Uncertain

1.0

DEOGEN2

Benign

0.060

Eigen

Uncertain

0.22

Eigen_PC

Benign

0.20

FATHMM_MKL

Benign

0.54

LIST_S2

Benign

0.79

M_CAP

Benign

0.0078

MetaRNN

Benign

0.31

MetaSVM

Benign

-1.0

MutationAssessor

Benign

1.4

PhyloP100

1.4

PrimateAI

Uncertain

0.59

PROVEAN

Benign

-2.0

REVEL

Benign

0.17

Sift

Uncertain

0.0070

Sift4G

Uncertain

0.027

Polyphen

0.98

Vest4

0.68

MutPred

0.23

Loss of ubiquitination at K73 (P = 0.0413)

MVP

0.42

MPC

0.022

ClinPred

0.18

GERP RS

3.8

Varity_R

0.22

gMVP

0.33

Mutation Taster

=82/18

polymorphism

(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

You must be logged in to view publications. This limit was set because tens of millions (!) of queries from AI bots are generated daily.

Variant summary

Frequency

Consequence

Scores

Clinical Significance

Conservation

Publications

ACMG classification

Variant Effect in Transcripts

RefSeq Transcripts

Ensembl Transcripts

Frequencies

Age Distribution

Age Distribution

ClinVar

Computational scores

Splicing

Publications

Other links and lift over