Genetic Variant NM_052939.4:c.2162A>G (chr1-157678753-T-C) – ACMG Classification: Benign (-20 pts)

Variant summary

Our verdict is Benign. The variant received -20 ACMG points: 0P and 20B. BP4_StrongBP6_Very_StrongBA1

The NM_052939.4(FCRL3):c.2162A>G(p.Asn721Ser) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0543 in 1,613,992 control chromosomes in the GnomAD database, including 2,539 homozygotes. In-silico tool predicts a benign outcome for this variant. 15/21 in silico tools predict a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★★).

Frequency

Genomes: 𝑓 0.054 ( 232 hom., cov: 31)

Exomes 𝑓: 0.054 ( 2307 hom. )

Consequence

FCRL3
NM_052939.4 missense

Scores

Clinical Significance

Benign criteria provided, multiple submitters, no conflicts B:2

Conservation

PhyloP100: -0.0180

Publications

33 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 -20 ACMG points.

BP4

Computational evidence support a benign effect (MetaRNN=0.0021958053).

BP6

Variant 1-157678753-T-C is Benign according to our data. Variant chr1-157678753-T-C is described in ClinVar as Benign. ClinVar VariationId is 1291670.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars.

BA1

GnomAd4 highest subpopulation (SAS) allele frequency at 95% confidence interval = 0.0659 is higher than 0.05.

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_052939.4. You can select a different transcript below to see updated ACMG assignments.

RefSeq Transcripts

Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
FCRL3	NM_052939.4	MANE Select	c.2162A>G	p.Asn721Ser	missense	Exon 15 of 15	NP_443171.2
FCRL3	NM_001320333.2		c.2162A>G	p.Asn721Ser	missense	Exon 15 of 16	NP_001307262.1	Q96P31-6
FCRL3	NR_135214.2		n.2384A>G		non_coding_transcript_exon	Exon 15 of 16

Ensembl Transcripts

Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
FCRL3	ENST00000368184.8	TSL:1 MANE Select	c.2162A>G	p.Asn721Ser	missense	Exon 15 of 15	ENSP00000357167.3	Q96P31-1
FCRL3	ENST00000368186.9	TSL:1	c.2162A>G	p.Asn721Ser	missense	Exon 15 of 16	ENSP00000357169.5	Q96P31-6
FCRL3	ENST00000473231.5	TSL:1	n.3004A>G		non_coding_transcript_exon	Exon 9 of 9

Frequencies

GnomAD3 genomes

AF:

0.0535

AC:

8143

AN:

152068

Hom.:

232

Cov.:

show subpopulations

Gnomad AFR

AF:

0.0617

Gnomad AMI

AF:

0.0208

Gnomad AMR

AF:

0.0410

Gnomad ASJ

AF:

0.0222

Gnomad EAS

AF:

0.0582

Gnomad SAS

AF:

0.0725

Gnomad FIN

AF:

0.0624

Gnomad MID

AF:

0.0158

Gnomad NFE

AF:

0.0509

Gnomad OTH

AF:

0.0402

GnomAD2 exomes

AF:

0.0544

AC:

13674

AN:

251392

AF XY:

0.0551

show subpopulations

Gnomad AFR exome

AF:

0.0627

Gnomad AMR exome

AF:

0.0463

Gnomad ASJ exome

AF:

0.0219

Gnomad EAS exome

AF:

0.0579

Gnomad FIN exome

AF:

0.0607

Gnomad NFE exome

AF:

0.0511

Gnomad OTH exome

AF:

0.0494

GnomAD4 exome

AF:

0.0543

AC:

79409

AN:

1461806

Hom.:

2307

Cov.:

AF XY:

0.0544

AC XY:

39595

AN XY:

727204

show subpopulations

African (AFR)

AF:

0.0631

AC:

2112

AN:

33476

American (AMR)

AF:

0.0454

AC:

2028

AN:

44704

Ashkenazi Jewish (ASJ)

AF:

0.0242

AC:

632

AN:

26136

East Asian (EAS)

AF:

0.0459

AC:

1822

AN:

39700

South Asian (SAS)

AF:

0.0760

AC:

6555

AN:

86256

European-Finnish (FIN)

AF:

0.0609

AC:

3253

AN:

53416

Middle Eastern (MID)

AF:

0.0413

AC:

237

AN:

5742

European-Non Finnish (NFE)

AF:

0.0537

AC:

59753

AN:

1111988

Other (OTH)

AF:

0.0500

AC:

3017

AN:

60388

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.497

Heterozygous variant carriers

4925

9850

14774

19699

24624

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Exome Het

Exome Hom

Variant carriers

2330

4660

6990

9320

11650

<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:

0.0536

AC:

8153

AN:

152186

Hom.:

232

Cov.:

AF XY:

0.0548

AC XY:

4079

AN XY:

74428

show subpopulations

African (AFR)

AF:

0.0617

AC:

2560

AN:

41520

American (AMR)

AF:

0.0410

AC:

626

AN:

15276

Ashkenazi Jewish (ASJ)

AF:

0.0222

AC:

AN:

3468

East Asian (EAS)

AF:

0.0580

AC:

300

AN:

5174

South Asian (SAS)

AF:

0.0721

AC:

348

AN:

4824

European-Finnish (FIN)

AF:

0.0624

AC:

662

AN:

10604

Middle Eastern (MID)

AF:

0.0170

AC:

AN:

294

European-Non Finnish (NFE)

AF:

0.0509

AC:

3463

AN:

68002

Other (OTH)

AF:

0.0440

AC:

AN:

2112

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.504

Heterozygous variant carriers

395

791

1186

1582

1977

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Genome Het

Genome Hom

Variant carriers

100

200

300

400

500

<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:

0.0511

Hom.:

974

Bravo

AF:

0.0517

TwinsUK

AF:

0.0539

AC:

200

ALSPAC

AF:

0.0540

AC:

208

ESP6500AA

AF:

0.0615

AC:

271

ESP6500EA

AF:

0.0515

AC:

443

ExAC

AF:

0.0561

AC:

6817

Asia WGS

AF:

0.0810

AC:

280

AN:

3478

EpiCase

AF:

0.0471

EpiControl

AF:

0.0492

ClinVar

ClinVar submissions

Significance:Benign

Revision:criteria provided, multiple submitters, no conflicts

View on ClinVar

Pathogenic

VUS

Benign

Condition

not provided (2)

Computational scores

Source: dbNSFP v4.9

Name

Calibrated prediction

Score

Prediction

AlphaMissense

Benign

0.11

BayesDel_addAF

Benign

-0.63

BayesDel_noAF

Benign

-0.62

CADD

Benign

3.0

(source)

DANN

Benign

0.81

DEOGEN2

Benign

0.0039

Eigen

Benign

-0.76

Eigen_PC

Benign

-0.85

FATHMM_MKL

Benign

0.035

LIST_S2

Benign

0.66

MetaRNN

Benign

0.0022

MetaSVM

Benign

-1.1

MutationAssessor

Benign

1.8

PhyloP100

-0.018

PrimateAI

Benign

0.39

PROVEAN

Benign

-0.79

REVEL

Benign

0.029

Sift

Benign

0.17

Sift4G

Benign

0.23

Polyphen

0.30

Vest4

0.048

MPC

0.0077

ClinPred

0.0022

GERP RS

1.0

Varity_R

0.069

gMVP

0.085

Mutation Taster

=98/2

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

Variant Effect in Transcripts

RefSeq Transcripts

Ensembl Transcripts

Frequencies

Age Distribution

Age Distribution

ClinVar

Computational scores

Splicing

Publications

Other links and lift over