Genetic Variant NM_001002901.4:c.1148G>A (chr1-161727529-G-A) – ACMG Classification: Benign (-12 pts)

Variant summary

Our verdict is Benign. The variant received -12 ACMG points: 0P and 12B. BP4_StrongBA1

The NM_001002901.4(FCRLB):c.1148G>A(p.Gly383Asp) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0802 in 1,614,042 control chromosomes in the GnomAD database, including 5,569 homozygotes. 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.

Frequency

Genomes: 𝑓 0.062 ( 381 hom., cov: 31)

Exomes 𝑓: 0.082 ( 5188 hom. )

Consequence

FCRLB
NM_001002901.4 missense

Scores

Clinical Significance

Not reported in ClinVar

Conservation

PhyloP100: 2.21

Publications

13 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: Benign. The variant received -12 ACMG points.

BP4

Computational evidence support a benign effect (MetaRNN=0.0016637743).

BA1

GnomAd4 highest subpopulation (NFE) allele frequency at 95% confidence interval = 0.0836 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
FCRLB	NM_001002901.4 link	c.1148G>A	p.Gly383Asp	missense_variant	Exon 8 of 8	ENST00000367948.7	NP_001002901.1	Q6BAA4-1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
FCRLB	ENST00000367948.7 link	c.1148G>A	p.Gly383Asp	missense_variant	Exon 8 of 8	1	NM_001002901.4	ENSP00000356925.2		Q6BAA4-1

Frequencies

GnomAD3 genomes

AF:

0.0618

AC:

9401

AN:

152038

Hom.:

380

Cov.:

show subpopulations

Gnomad AFR

AF:

0.0175

Gnomad AMI

AF:

0.0186

Gnomad AMR

AF:

0.0682

Gnomad ASJ

AF:

0.0715

Gnomad EAS

AF:

0.0789

Gnomad SAS

AF:

0.0511

Gnomad FIN

AF:

0.0708

Gnomad MID

AF:

0.0475

Gnomad NFE

AF:

0.0854

Gnomad OTH

AF:

0.0690

GnomAD2 exomes

AF:

0.0734

AC:

18377

AN:

250496

AF XY:

0.0734

show subpopulations

Gnomad AFR exome

AF:

0.0160

Gnomad AMR exome

AF:

0.0743

Gnomad ASJ exome

AF:

0.0764

Gnomad EAS exome

AF:

0.0776

Gnomad FIN exome

AF:

0.0695

Gnomad NFE exome

AF:

0.0872

Gnomad OTH exome

AF:

0.0802

GnomAD4 exome

AF:

0.0821

AC:

120033

AN:

1461886

Hom.:

5188

Cov.:

AF XY:

0.0808

AC XY:

58776

AN XY:

727244

show subpopulations

African (AFR)

AF:

0.0144

AC:

481

AN:

33480

American (AMR)

AF:

0.0727

AC:

3252

AN:

44724

Ashkenazi Jewish (ASJ)

AF:

0.0716

AC:

1871

AN:

26136

East Asian (EAS)

AF:

0.0974

AC:

3865

AN:

39700

South Asian (SAS)

AF:

0.0486

AC:

4196

AN:

86258

European-Finnish (FIN)

AF:

0.0733

AC:

3915

AN:

53416

Middle Eastern (MID)

AF:

0.0437

AC:

252

AN:

5768

European-Non Finnish (NFE)

AF:

0.0878

AC:

97673

AN:

1112008

Other (OTH)

AF:

0.0750

AC:

4528

AN:

60396

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.479

Heterozygous variant carriers

7486

14973

22459

29946

37432

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Exome Het

Exome Hom

Variant carriers

3570

7140

10710

14280

17850

<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:

0.0618

AC:

9397

AN:

152156

Hom.:

381

Cov.:

AF XY:

0.0611

AC XY:

4543

AN XY:

74382

show subpopulations

African (AFR)

AF:

0.0174

AC:

723

AN:

41542

American (AMR)

AF:

0.0681

AC:

1042

AN:

15292

Ashkenazi Jewish (ASJ)

AF:

0.0715

AC:

248

AN:

3470

East Asian (EAS)

AF:

0.0792

AC:

407

AN:

5136

South Asian (SAS)

AF:

0.0508

AC:

244

AN:

4806

European-Finnish (FIN)

AF:

0.0708

AC:

751

AN:

10606

Middle Eastern (MID)

AF:

0.0408

AC:

AN:

294

European-Non Finnish (NFE)

AF:

0.0854

AC:

5809

AN:

67988

Other (OTH)

AF:

0.0682

AC:

144

AN:

2110

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.494

Heterozygous variant carriers

439

878

1318

1757

2196

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Genome Het

Genome Hom

Variant carriers

118

236

354

472

590

<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:

0.0789

Hom.:

1713

Bravo

AF:

0.0611

TwinsUK

AF:

0.0914

AC:

339

ALSPAC

AF:

0.0991

AC:

382

ESP6500AA

AF:

0.0161

AC:

ESP6500EA

AF:

0.0883

AC:

759

ExAC

AF:

0.0713

AC:

8659

Asia WGS

AF:

0.0800

AC:

276

AN:

3478

EpiCase

AF:

0.0833

EpiControl

AF:

0.0847

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

AlphaMissense

Benign

0.095

BayesDel_addAF

Benign

-0.64

BayesDel_noAF

Benign

-0.58

CADD

Benign

(source)

DANN

Uncertain

1.0

DEOGEN2

Benign

0.048

Eigen

Benign

0.074

Eigen_PC

Benign

0.027

FATHMM_MKL

Benign

0.53

LIST_S2

Benign

0.52

MetaRNN

Benign

0.0017

MetaSVM

Benign

-0.81

MutationAssessor

Uncertain

2.1

PhyloP100

2.2

PrimateAI

Benign

0.41

PROVEAN

Benign

-1.7

REVEL

Benign

0.080

Sift

Benign

0.056

Sift4G

Benign

0.16

Polyphen

0.96

Vest4

0.072

MPC

0.99

ClinPred

0.073

GERP RS

2.4

Varity_R

0.19

gMVP

0.48

Mutation Taster

=100/0

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