Genetic Variant FCRLB:p.Ala270Ser (chr1-161726936-G-T) – ACMG Classification: Uncertain_significance (0 pts)

Variant summary

Our verdict is Uncertain significance. The variant received 0 ACMG points: 2P and 2B. PM2BP4_Moderate

The NM_001002901.4(FCRLB):c.808G>T(p.Ala270Ser) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.000000711 in 1,406,242 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a benign outcome for this variant. 13/21 in silico tools predict a benign outcome for this variant. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar. Another variant affecting the same amino acid position, but resulting in a different missense (i.e. A270P) has been classified as Uncertain significance.

Frequency

Genomes: not found (cov: 32)

Exomes 𝑓: 7.1e-7 ( 0 hom. )

Consequence

FCRLB
NM_001002901.4 missense

Scores

Clinical Significance

Not reported in ClinVar

Conservation

PhyloP100: 2.81

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:

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ACMG classification

Classification was made for transcript

Our verdict: Uncertain_significance. The variant received 0 ACMG points.

PM2

Very rare variant in population databases, with high coverage;

BP4

Computational evidence support a benign effect (MetaRNN=0.200079).

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.808G>T	p.Ala270Ser	missense	Exon 7 of 8	NP_001002901.1	Q6BAA4-1
FCRLB	NM_001320241.1		c.808G>T	p.Ala270Ser	missense	Exon 6 of 7	NP_001307170.1	Q6BAA4-1
FCRLB	NM_001288831.1		c.704G>T	p.Gly235Val	missense	Exon 5 of 6	NP_001275760.1	Q6BAA4-2

Ensembl Transcripts

Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
FCRLB	ENST00000367948.7	TSL:1 MANE Select	c.808G>T	p.Ala270Ser	missense	Exon 7 of 8	ENSP00000356925.2	Q6BAA4-1
FCRLB	ENST00000336830.9	TSL:1	c.704G>T	p.Gly235Val	missense	Exon 5 of 6	ENSP00000338598.5	Q6BAA4-2
FCRLB	ENST00000367944.3	TSL:1	c.683G>T	p.Gly228Val	missense	Exon 4 of 5	ENSP00000356921.3	Q6BAA4-3

Frequencies

GnomAD3 genomes

Cov.:

GnomAD4 exome

AF:

7.11e-7

AC:

AN:

1406242

Hom.:

Cov.:

AF XY:

0.00000144

AC XY:

AN XY:

693572

show subpopulations

⚠️ The allele balance in gnomAD version 4 Exomes is significantly skewed from the expected value of 0.5.

African (AFR)

AF:

0.00

AC:

AN:

31554

American (AMR)

AF:

0.00

AC:

AN:

37144

Ashkenazi Jewish (ASJ)

AF:

0.00

AC:

AN:

23396

East Asian (EAS)

AF:

0.00

AC:

AN:

38308

South Asian (SAS)

AF:

0.00

AC:

AN:

79852

European-Finnish (FIN)

AF:

0.00

AC:

AN:

50490

Middle Eastern (MID)

AF:

0.00

AC:

AN:

4884

European-Non Finnish (NFE)

AF:

0.00

AC:

AN:

1082980

Other (OTH)

AF:

0.0000174

AC:

AN:

57634

⚠️ The allele balance in gnomAD4 Exomes is highly skewed from 0.5 (p-value = 0), which strongly suggests a high chance of mosaicism in these individuals.

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.225

Heterozygous variant carriers

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

GnomAD4 genome

Cov.:

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name

Calibrated prediction

Score

Prediction

AlphaMissense

Benign

0.12

BayesDel_addAF

Uncertain

0.092

BayesDel_noAF

Benign

-0.11

CADD

Benign

(source)

DANN

Uncertain

1.0

DEOGEN2

Benign

0.050

Eigen

Benign

-0.28

Eigen_PC

Benign

-0.28

FATHMM_MKL

Benign

0.15

LIST_S2

Benign

0.49

M_CAP

Benign

0.060

MetaRNN

Benign

0.20

MetaSVM

Benign

-0.95

PhyloP100

2.8

PrimateAI

Uncertain

0.75

PROVEAN

Benign

-1.2

REVEL

Benign

0.27

Sift

Uncertain

0.0010

Sift4G

Uncertain

0.012

Polyphen

0.49

Vest4

0.32

MutPred

0.22

Gain of glycosylation at A270 (P = 0.0328)

MVP

0.63

MPC

1.4

ClinPred

0.99

GERP RS

3.7

Varity_R

0.25

gMVP

0.26

Mutation Taster

=94/6

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

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Variant summary

Frequency

Consequence

Scores

Clinical Significance

Conservation

Publications

ACMG classification

Variant Effect in Transcripts

RefSeq Transcripts

Ensembl Transcripts

Frequencies

ClinVar

Computational scores

Splicing

Publications

Other links and lift over