rs944627

chr1-157680749-G-A

Variant summary

Our verdict is Benign. Variant got -12 ACMG points: 0P and 12B. BP4_Strong BA1

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. 14/20 in silico tools predict a benign outcome for this variant. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar. Another nucleotide change resulting in same amino acid change has been previously reported as Likely benignin UniProt.

• Frequency:
  • Genomes: 𝑓 0.039 (368 hom., cov: 32)
  • Exomes 𝑓: 0.0041 (356 hom.)
• Consequence: FCRL3 NM_052939.4 missense
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 1.08

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]

ACMG classification

Verdict is Benign. Variant got -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/exons	MANE	UniProt
FCRL3	NM_052939.4	c.1979C>T	p.Pro660Leu	missense_variant	13/15	ENST00000368184.8

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
FCRL3	ENST00000368184.8	c.1979C>T	p.Pro660Leu	missense_variant	13/15	1	NM_052939.4	P2

Frequencies

GnomAD3 genomes AF: 0.0390 AC: 5934 AN: 152170 Hom.: 364 Cov.: 32

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

GnomAD3 exomes AF: 0.0104 AC: 2613 AN: 251222 Hom.: 167 AF XY: 0.00738 AC XY: 1002 AN XY: 135774

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 SAS exome AF: 0.000523

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.: 31 AF XY: 0.00360 AC XY: 2621 AN XY: 727154

Gnomad4 AFR exome AF: 0.141

Gnomad4 AMR exome AF: 0.00792

Gnomad4 ASJ exome AF: 0.00

Gnomad4 EAS exome AF: 0.0000504

Gnomad4 SAS exome AF: 0.000800

Gnomad4 FIN exome AF: 0.00

Gnomad4 NFE exome AF: 0.000159

Gnomad4 OTH exome AF: 0.00987

GnomAD4 genome AF: 0.0391 AC: 5957 AN: 152288 Hom.: 368 Cov.: 32 AF XY: 0.0375 AC XY: 2791 AN XY: 74452

Gnomad4 AFR AF: 0.135

Gnomad4 AMR AF: 0.0160

Gnomad4 ASJ AF: 0.00

Gnomad4 EAS AF: 0.00

Gnomad4 SAS AF: 0.00186

Gnomad4 FIN AF: 0.00

Gnomad4 NFE AF: 0.000353

Gnomad4 OTH AF: 0.0346

Alfa AF: 0.00892 Hom.: 142

Bravo AF: 0.0441

TwinsUK AF: 0.00135 AC: 5

ALSPAC AF: 0.000778 AC: 3

ESP6500AA AF: 0.133 AC: 586

ESP6500EA AF: 0.000814 AC: 7

ExAC AF: 0.0125 AC: 1522

Asia WGS AF: 0.0110 AC: 37 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	T
BayesDel_noAF	Benign	-0.71
Cadd	Benign	0.12
Dann	Benign	0.44
Eigen	Benign	-1.9
Eigen_PC	Benign	-1.8
FATHMM_MKL	Benign	0.00014	N
LIST_S2	Benign	0.21	T;T
MetaRNN	Benign	0.0016	T;T
MetaSVM	Benign	-1.0	T
MutationAssessor	Benign	-2.4	N;N
MutationTaster	Benign	1.0	P;P;P
PrimateAI	Benign	0.30	T
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	T
GERP RS		-1.3
Varity_R		0.041
gMVP		0.062

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: rs944627; hg19: chr1-157650539;