Genetic Variant NM_001002901.4:c.673C>T (chr1-161726801-C-T) – ACMG Classification: Uncertain_significance (2 pts)

Variant summary

Our verdict is Uncertain significance. The variant received 2 ACMG points: 2P and 0B. PM2

The NM_001002901.4(FCRLB):c.673C>T(p.Pro225Ser) variant causes a missense change. The variant allele was found at a frequency of 0.00000895 in 1,563,618 control chromosomes in the GnomAD database, with no homozygous occurrence. Variant has been reported in ClinVar as Uncertain significance (★).

Frequency

Genomes: 𝑓 0.0000066 ( 0 hom., cov: 32)

Exomes 𝑓: 0.0000092 ( 0 hom. )

Consequence

FCRLB
NM_001002901.4 missense

Scores

Clinical Significance

Uncertain significance criteria provided, single submitter U:1

Conservation

PhyloP100: 3.81

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 2 ACMG points.

PM2

Very rare variant in population databases, with high coverage;

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.673C>T	p.Pro225Ser	missense	Exon 7 of 8	NP_001002901.1	Q6BAA4-1
FCRLB	NM_001320241.1		c.673C>T	p.Pro225Ser	missense	Exon 6 of 7	NP_001307170.1	Q6BAA4-1
FCRLB	NM_001288829.1		c.575-47C>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.673C>T	p.Pro225Ser	missense	Exon 7 of 8	ENSP00000356925.2	Q6BAA4-1
FCRLB	ENST00000367946.7	TSL:1	c.575-47C>T		intron	N/A	ENSP00000356923.3	Q6BAA4-4
FCRLB	ENST00000367945.5	TSL:1	c.554-47C>T		intron	N/A	ENSP00000356922.1	Q6BAA4-5

Frequencies

GnomAD3 genomes

AF:

0.00000657

AC:

AN:

152214

Hom.:

Cov.:

show subpopulations

Gnomad AFR

AF:

0.0000241

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:

0.0000304

AC:

AN:

164274

AF XY:

0.0000110

show subpopulations

Gnomad AFR exome

AF:

0.00

Gnomad AMR exome

AF:

0.000114

Gnomad ASJ exome

AF:

0.00

Gnomad EAS exome

AF:

0.000154

Gnomad FIN exome

AF:

0.00

Gnomad NFE exome

AF:

0.00

Gnomad OTH exome

AF:

0.00

GnomAD4 exome

AF:

0.00000921

AC:

AN:

1411404

Hom.:

Cov.:

AF XY:

0.00000573

AC XY:

AN XY:

698110

show subpopulations

African (AFR)

AF:

0.00

AC:

AN:

32108

American (AMR)

AF:

0.0000793

AC:

AN:

37838

Ashkenazi Jewish (ASJ)

AF:

0.00

AC:

AN:

24326

East Asian (EAS)

AF:

0.000187

AC:

AN:

37520

South Asian (SAS)

AF:

0.00

AC:

AN:

79894

European-Finnish (FIN)

AF:

0.00

AC:

AN:

48470

Middle Eastern (MID)

AF:

0.00

AC:

AN:

4700

European-Non Finnish (NFE)

AF:

0.00000276

AC:

AN:

1088350

Other (OTH)

AF:

0.00

AC:

AN:

58198

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.490

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:

0.00000657

AC:

AN:

152214

Hom.:

Cov.:

AF XY:

0.00

AC XY:

AN XY:

74356

show subpopulations

African (AFR)

AF:

0.0000241

AC:

AN:

41456

American (AMR)

AF:

0.00

AC:

AN:

15286

Ashkenazi Jewish (ASJ)

AF:

0.00

AC:

AN:

3472

East Asian (EAS)

AF:

0.00

AC:

AN:

5184

South Asian (SAS)

AF:

0.00

AC:

AN:

4838

European-Finnish (FIN)

AF:

0.00

AC:

AN:

10632

Middle Eastern (MID)

AF:

0.00

AC:

AN:

316

European-Non Finnish (NFE)

AF:

0.00

AC:

AN:

68026

Other (OTH)

AF:

0.00

AC:

AN:

2092

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.575

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:

0.00

Hom.:

Bravo

AF:

0.0000113

ExAC

AF:

0.0000172

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

0.13

BayesDel_addAF

Benign

-0.024

BayesDel_noAF

Uncertain

-0.010

CADD

Pathogenic

(source)

DANN

Uncertain

1.0

DEOGEN2

Benign

0.35

Eigen

Uncertain

0.60

Eigen_PC

Uncertain

0.54

FATHMM_MKL

Benign

0.51

LIST_S2

Benign

0.65

M_CAP

Pathogenic

0.61

MetaRNN

Uncertain

0.73

MetaSVM

Pathogenic

1.0

MutationAssessor

Pathogenic

3.1

PhyloP100

3.8

PrimateAI

Pathogenic

0.82

PROVEAN

Uncertain

-4.3

REVEL

Uncertain

0.55

Sift

Benign

0.54

Sift4G

Uncertain

0.056

Polyphen

1.0

Vest4

0.56

MutPred

0.32

Gain of MoRF binding (P = 0.0461)

MVP

0.85

MPC

1.5

ClinPred

0.73

GERP RS

4.4

Varity_R

0.31

gMVP

0.48

Mutation Taster

=79/21

polymorphism

(source)

Splicing

Name

Calibrated prediction

Score

Prediction

SpliceAI score (max)

0.030

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