1-157678753-T-C

Position:

• chr1-157678753-T-C

Variant summary

Our verdict is Benign. Variant got -20 ACMG points: 0P and 20B. BP4_Strong BP6_Very_Strong BA1

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 same amino acid change has been previously reported as Likely benignin UniProt.

• Frequency:
  • Genomes: 𝑓 0.054 (232 hom., cov: 31)
  • Exomes 𝑓: 0.054 (2307 hom.)
• Consequence: FCRL3 NM_052939.4 missense
• Clinical Significance: Benign criteria provided, multiple submitters, no conflicts B:2
• Conservation: PhyloP100: -0.0180

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 (HGNC:):

ACMG classification

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	c.2162A>G	p.Asn721Ser	missense_variant	15/15	ENST00000368184.8	NP_443171.2

Ensembl

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

Frequencies

GnomAD3 genomes AF: 0.0535 AC: 8143 AN: 152068 Hom.: 232 Cov.: 31

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

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.: 34 AF XY: 0.0544 AC XY: 39595 AN XY: 727204

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.: 31 AF XY: 0.0548 AC XY: 4079 AN XY: 74428

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

Submissions by phenotype

not provided Benign:2

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

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
AlphaMissense	Benign	0.11
BayesDel_addAF	Benign	-0.63	T
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	N
LIST_S2	Benign	0.66	T;T
MetaRNN	Benign	0.0022	T;T
MetaSVM	Benign	-1.1	T
MutationAssessor	Benign	1.8	L;L
MutationTaster	Benign	1.0	P;P;P
PrimateAI	Benign	0.39	T
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	T
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

Other links and lift over

dbSNP: rs2282284; hg19: chr1-157648543; COSMIC: COSV63843869; COSMIC: COSV63843869;