Variant chr1-157678753-T-C details in Genebe, Genetics Data Aggregator

Variant summary

Our verdict is Benign. Variant got -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. 14/20 in silico tools predict a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★★). Another nucleotide change resulting in the same amino acid substitution has been previously reported as Likely benign in UniProt.

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

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 made for transcript

Verdict is Benign. Variant got -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 id 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.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
FCRL3	NM_052939.4 link	c.2162A>G	p.Asn721Ser	missense_variant	15/15	ENST00000368184.8	NP_443171.2	Q96P31-1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
FCRL3	ENST00000368184.8 link	c.2162A>G	p.Asn721Ser	missense_variant	15/15	1	NM_052939.4	ENSP00000357167.3		Q96P31-1

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

GnomAD3 exomes

AF:

0.0544

AC:

13674

AN:

251392

Hom.:

406

AF XY:

0.0551

AC XY:

7492

AN XY:

135862

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 SAS exome

AF:

0.0765

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

Gnomad4 AFR exome

AF:

0.0631

Gnomad4 AMR exome

AF:

0.0454

Gnomad4 ASJ exome

AF:

0.0242

Gnomad4 EAS exome

AF:

0.0459

Gnomad4 SAS exome

AF:

0.0760

Gnomad4 FIN exome

AF:

0.0609

Gnomad4 NFE exome

AF:

0.0537

Gnomad4 OTH exome

AF:

0.0500

GnomAD4 genome

AF:

0.0536

AC:

8153

AN:

152186

Hom.:

232

Cov.:

AF XY:

0.0548

AC XY:

4079

AN XY:

74428

show subpopulations

Gnomad4 AFR

AF:

0.0617

Gnomad4 AMR

AF:

0.0410

Gnomad4 ASJ

AF:

0.0222

Gnomad4 EAS

AF:

0.0580

Gnomad4 SAS

AF:

0.0721

Gnomad4 FIN

AF:

0.0624

Gnomad4 NFE

AF:

0.0509

Gnomad4 OTH

AF:

0.0440

Alfa

AF:

0.0497

Hom.:

524

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

Significance: Benign

Submissions summary: Benign:2

Revision: criteria provided, multiple submitters, no conflicts

LINK: link

Submissions by phenotype

not provided

Benign:2

Benign, criteria provided, single submitter	not provided	Breakthrough Genomics, Breakthrough Genomics	-	- -
Benign, criteria provided, single submitter	clinical testing	GeneDx	Feb 24, 2021	This variant is associated with the following publications: (PMID: 25862376, 26402798) -

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

AlphaMissense

Benign

0.11

BayesDel_addAF

Benign

-0.63

BayesDel_noAF

Benign

-0.62

CADD

Benign

3.0

DANN

Benign

0.81

DEOGEN2

Benign

0.0039

.;T

Eigen

Benign

-0.76

Eigen_PC

Benign

-0.85

FATHMM_MKL

Benign

0.035

LIST_S2

Benign

0.66

T;T

MetaRNN

Benign

0.0022

T;T

MetaSVM

Benign

-1.1

MutationAssessor

Benign

1.8

L;L

PrimateAI

Benign

0.39

PROVEAN

Benign

-0.79

N;N

REVEL

Benign

0.029

Sift

Benign

0.17

T;T

Sift4G

Benign

0.23

T;T

Polyphen

0.30

B;B

Vest4

0.048

MPC

0.0077

ClinPred

0.0022

GERP RS

1.0

Varity_R

0.069

gMVP

0.085

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

LitVar

Below is the list of publications found by LitVar. It may be empty.

Variant summary

Frequency

Consequence

Scores

Clinical Significance

Conservation

ACMG classification

Transcripts

RefSeq

Ensembl

Frequencies

ClinVar

Submissions by phenotype

Computational scores

Splicing

Publications

LitVar

Other links and lift over