Genetic Variant FCRLB:p.His224Tyr (chr1-161726798-C-T) – ACMG Classification: Uncertain_significance (0 pts)

Variant summary

Our verdict is Uncertain significance. The variant received 0 ACMG points: 0P and 0B.

The NM_001002901.4(FCRLB):c.670C>T(p.His224Tyr) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.000309 in 1,564,418 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 (★). Another variant affecting the same amino acid position, but resulting in a different missense (i.e. H224Q) has been classified as Uncertain significance.

Frequency

Genomes: 𝑓 0.00043 ( 0 hom., cov: 32)

Exomes 𝑓: 0.00030 ( 1 hom. )

Consequence

FCRLB
NM_001002901.4 missense

Scores

Clinical Significance

Uncertain significance criteria provided, single submitter U:1

Conservation

PhyloP100: 2.34

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: Uncertain_significance. The variant received 0 ACMG points.

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.670C>T	p.His224Tyr	missense	Exon 7 of 8	NP_001002901.1	Q6BAA4-1
FCRLB	NM_001320241.1		c.670C>T	p.His224Tyr	missense	Exon 6 of 7	NP_001307170.1	Q6BAA4-1
FCRLB	NM_001288829.1		c.575-50C>T		intron	N/A	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.670C>T	p.His224Tyr	missense	Exon 7 of 8	ENSP00000356925.2	Q6BAA4-1
FCRLB	ENST00000367946.7	TSL:1	c.575-50C>T		intron	N/A	ENSP00000356923.3	Q6BAA4-4
FCRLB	ENST00000367945.5	TSL:1	c.554-50C>T		intron	N/A	ENSP00000356922.1	Q6BAA4-5

Frequencies

GnomAD3 genomes

AF:

0.000427

AC:

AN:

152202

Hom.:

Cov.:

show subpopulations

Gnomad AFR

AF:

0.00

Gnomad AMI

AF:

0.00987

Gnomad AMR

AF:

0.000131

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:

0.000794

Gnomad OTH

AF:

0.00

GnomAD2 exomes

AF:

0.000218

AC:

AN:

165084

AF XY:

0.000209

show subpopulations

Gnomad AFR exome

AF:

0.00

Gnomad AMR exome

AF:

0.00

Gnomad ASJ exome

AF:

0.000279

Gnomad EAS exome

AF:

0.00

Gnomad FIN exome

AF:

0.00

Gnomad NFE exome

AF:

0.000506

Gnomad OTH exome

AF:

0.00

GnomAD4 exome

AF:

0.000297

AC:

419

AN:

1412216

Hom.:

Cov.:

AF XY:

0.000321

AC XY:

224

AN XY:

698614

show subpopulations

African (AFR)

AF:

0.00

AC:

AN:

32152

American (AMR)

AF:

0.0000263

AC:

AN:

38052

Ashkenazi Jewish (ASJ)

AF:

0.000124

AC:

AN:

24266

East Asian (EAS)

AF:

0.00

AC:

AN:

37616

South Asian (SAS)

AF:

0.00

AC:

AN:

79862

European-Finnish (FIN)

AF:

0.0000207

AC:

AN:

48324

Middle Eastern (MID)

AF:

0.00

AC:

AN:

4718

European-Non Finnish (NFE)

AF:

0.000374

AC:

407

AN:

1088970

Other (OTH)

AF:

0.000120

AC:

AN:

58256

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.496

Heterozygous variant carriers

121

151

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:

0.000427

AC:

AN:

152202

Hom.:

Cov.:

AF XY:

0.000498

AC XY:

AN XY:

74356

show subpopulations

African (AFR)

AF:

0.00

AC:

AN:

41456

American (AMR)

AF:

0.000131

AC:

AN:

15290

Ashkenazi Jewish (ASJ)

AF:

0.00

AC:

AN:

3472

East Asian (EAS)

AF:

0.00

AC:

AN:

5180

South Asian (SAS)

AF:

0.00

AC:

AN:

4830

European-Finnish (FIN)

AF:

0.00

AC:

AN:

10630

Middle Eastern (MID)

AF:

0.00

AC:

AN:

316

European-Non Finnish (NFE)

AF:

0.000794

AC:

AN:

68022

Other (OTH)

AF:

0.00

AC:

AN:

2094

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.493

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:

0.000776

Hom.:

Bravo

AF:

0.000344

ExAC

AF:

0.000216

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

Benign

0.18

BayesDel_addAF

Benign

-0.12

BayesDel_noAF

Uncertain

0.010

CADD

Pathogenic

(source)

DANN

Uncertain

0.98

DEOGEN2

Benign

0.048

Eigen

Uncertain

0.31

Eigen_PC

Uncertain

0.31

FATHMM_MKL

Benign

0.41

LIST_S2

Benign

0.61

M_CAP

Pathogenic

0.46

MetaRNN

Benign

0.045

MetaSVM

Uncertain

0.57

MutationAssessor

Uncertain

2.6

PhyloP100

2.3

PrimateAI

Pathogenic

0.81

PROVEAN

Benign

-1.1

REVEL

Uncertain

0.47

Sift

Benign

1.0

Sift4G

Benign

0.29

Polyphen

0.98

Vest4

0.37

MVP

0.71

MPC

1.5

ClinPred

0.26

GERP RS

4.5

Varity_R

0.18

gMVP

0.41

Mutation Taster

=85/15

polymorphism

(source)

Splicing

Name

Calibrated prediction

Score

Prediction

SpliceAI score (max)

0.35

Details are displayed if max score is > 0.2

DS_AG_spliceai

0.35

Position offset: 9

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

Variant Effect in Transcripts

RefSeq Transcripts

Ensembl Transcripts

Frequencies

Age Distribution

Age Distribution

ClinVar

Computational scores

Splicing

Publications

Other links and lift over