dbSNP rs944627: FCRL3:p.Pro660Leu (chr1-157680749-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_052939.4(FCRL3):c.1979C>T(p.Pro660Leu) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00739 in 1,613,942 control chromosomes in the GnomAD database, including 724 homozygotes. In-silico tool predicts a benign outcome for this variant. 15/21 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 0.039 ( 368 hom., cov: 32)

Exomes 𝑓: 0.0041 ( 356 hom. )

Consequence

FCRL3
NM_052939.4 missense

Scores

Clinical Significance

Not reported in ClinVar

Conservation

PhyloP100: 1.08

Publications

13 publications found

Variant links:

Genes affected

FCRL3 (HGNC:18506): (Fc receptor like 3) This gene encodes a member of the immunoglobulin receptor superfamily and is one of several Fc receptor-like glycoproteins clustered on the long arm of chromosome 1. The encoded protein contains immunoreceptor-tyrosine activation motifs and immunoreceptor-tyrosine inhibitory motifs in its cytoplasmic domain and may play a role in regulation of the immune system. Mutations in this gene have been associated with rheumatoid arthritis, autoimmune thyroid disease, and systemic lupus erythematosus. Alternative splicing results in multiple transcript variants. [provided by RefSeq, Feb 2016]

FCRL3 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=0.0016227961).

BA1

GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.132 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
FCRL3	NM_052939.4 link	c.1979C>T	p.Pro660Leu	missense_variant	Exon 13 of 15	ENST00000368184.8	NP_443171.2	Q96P31-1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
FCRL3	ENST00000368184.8 link	c.1979C>T	p.Pro660Leu	missense_variant	Exon 13 of 15	1	NM_052939.4	ENSP00000357167.3		Q96P31-1

Frequencies

GnomAD3 genomes

AF:

0.0390

AC:

5934

AN:

152170

Hom.:

364

Cov.:

show subpopulations

Gnomad AFR

AF:

0.134

Gnomad AMI

AF:

0.00

Gnomad AMR

AF:

0.0160

Gnomad ASJ

AF:

0.00

Gnomad EAS

AF:

0.00

Gnomad SAS

AF:

0.00186

Gnomad FIN

AF:

0.00

Gnomad MID

AF:

0.0348

Gnomad NFE

AF:

0.000353

Gnomad OTH

AF:

0.0349

GnomAD2 exomes

AF:

0.0104

AC:

2613

AN:

251222

AF XY:

0.00738

show subpopulations

Gnomad AFR exome

AF:

0.140

Gnomad AMR exome

AF:

0.00738

Gnomad ASJ exome

AF:

0.00

Gnomad EAS exome

AF:

0.0000544

Gnomad FIN exome

AF:

0.00

Gnomad NFE exome

AF:

0.000370

Gnomad OTH exome

AF:

0.00327

GnomAD4 exome

AF:

0.00409

AC:

5974

AN:

1461654

Hom.:

356

Cov.:

AF XY:

0.00360

AC XY:

2621

AN XY:

727154

show subpopulations

African (AFR)

AF:

0.141

AC:

4703

AN:

33412

American (AMR)

AF:

0.00792

AC:

354

AN:

44698

Ashkenazi Jewish (ASJ)

AF:

0.00

AC:

AN:

26132

East Asian (EAS)

AF:

0.0000504

AC:

AN:

39692

South Asian (SAS)

AF:

0.000800

AC:

AN:

86244

European-Finnish (FIN)

AF:

0.00

AC:

AN:

53410

Middle Eastern (MID)

AF:

0.0127

AC:

AN:

5764

European-Non Finnish (NFE)

AF:

0.000159

AC:

177

AN:

1111916

Other (OTH)

AF:

0.00987

AC:

596

AN:

60386

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.439

Heterozygous variant carriers

272

545

817

1090

1362

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Exome Het

Exome Hom

Variant carriers

150

300

450

600

750

<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:

0.0391

AC:

5957

AN:

152288

Hom.:

368

Cov.:

AF XY:

0.0375

AC XY:

2791

AN XY:

74452

show subpopulations

African (AFR)

AF:

0.135

AC:

5594

AN:

41550

American (AMR)

AF:

0.0160

AC:

245

AN:

15306

Ashkenazi Jewish (ASJ)

AF:

0.00

AC:

AN:

3472

East Asian (EAS)

AF:

0.00

AC:

AN:

5182

South Asian (SAS)

AF:

0.00186

AC:

AN:

4826

European-Finnish (FIN)

AF:

0.00

AC:

AN:

10616

Middle Eastern (MID)

AF:

0.0408

AC:

AN:

294

European-Non Finnish (NFE)

AF:

0.000353

AC:

AN:

68018

Other (OTH)

AF:

0.0346

AC:

AN:

2112

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.504

Heterozygous variant carriers

277

553

830

1106

1383

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Genome Het

Genome Hom

Variant carriers

116

174

232

290

<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:

0.0152

Hom.:

335

Bravo

AF:

0.0441

TwinsUK

AF:

0.00135

AC:

ALSPAC

AF:

0.000778

AC:

ESP6500AA

AF:

0.133

AC:

586

ESP6500EA

AF:

0.000814

AC:

ExAC

AF:

0.0125

AC:

1522

Asia WGS

AF:

0.0110

AC:

AN:

3478

EpiCase

AF:

0.000218

EpiControl

AF:

0.000652

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

AlphaMissense

Benign

0.060

BayesDel_addAF

Benign

-0.73

BayesDel_noAF

Benign

-0.71

CADD

Benign

0.12

(source)

DANN

Benign

0.44

DEOGEN2

Benign

0.00077

.;T

Eigen

Benign

-1.9

Eigen_PC

Benign

-1.8

FATHMM_MKL

Benign

0.00014

LIST_S2

Benign

0.21

T;T

MetaRNN

Benign

0.0016

T;T

MetaSVM

Benign

-1.0

MutationAssessor

Benign

-2.4

N;N

PhyloP100

1.1

PrimateAI

Benign

0.30

PROVEAN

Benign

1.6

N;N

REVEL

Benign

0.070

Sift

Benign

1.0

T;T

Sift4G

Benign

0.77

T;T

Polyphen

0.0

B;B

Vest4

0.027

MPC

0.0063

ClinPred

0.0048

GERP RS

-1.3

Varity_R

0.041

gMVP

0.062

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