rs2290834

Positions:

• chr1-161629781-T-C

Variant summary

Our verdict is Benign. Variant got -12 ACMG points: 0P and 12B. BP4_Strong BP6_Very_Strong

The NM_001244753.2(FCGR3B):​c.316A>G​(p.Ile106Val) variant causes a missense change involving the alteration of a non-conserved nucleotide. In-silico tool predicts a benign outcome for this variant. 13/18 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 0.017 (4 hom., cov: 9)
  • Exomes 𝑓: 0.24 (50997 hom.)
  • Failed GnomAD Quality Control
• Consequence: FCGR3B NM_001244753.2 missense
• Clinical Significance: Benign criteria provided, multiple submitters, no conflicts B:2
• Conservation: PhyloP100: -6.08

Genes affected

FCGR3B (HGNC:3620): (Fc gamma receptor IIIb) The protein encoded by this gene is a low affinity receptor for the Fc region of gamma immunoglobulins (IgG). The encoded protein acts as a monomer and can bind either monomeric or aggregated IgG. This gene may function to capture immune complexes in the peripheral circulation. Several transcript variants encoding different isoforms have been found for this gene. A highly-similar gene encoding a related protein is also found on chromosome 1. [provided by RefSeq, Aug 2012]

ACMG classification

Verdict is Benign. Variant got -12 ACMG points.

• BP4: Computational evidence support a benign effect (MetaRNN=0.005424112).
• BP6: Variant 1-161629781-T-C is Benign according to our data. Variant chr1-161629781-T-C is described in ClinVar as [Benign]. Clinvar id is 402858.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars. Variant chr1-161629781-T-C is described in Lovd as [Benign].

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
FCGR3B	NM_001244753.2	c.316A>G	p.Ile106Val	missense_variant	3/5	ENST00000650385.1	NP_001231682.2

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
FCGR3B	ENST00000650385.1	c.316A>G	p.Ile106Val	missense_variant	3/5		NM_001244753.2	ENSP00000497461	P2

Frequencies

GnomAD3 genomes AF: 0.00 AC: 1082 AN: 65610 Hom.: 4 Cov.: 9 FAILED QC

Gnomad AFR AF: 0.00925

Gnomad AMI AF: 0.0255

Gnomad AMR AF: 0.0243

Gnomad ASJ AF: 0.00806

Gnomad EAS AF: 0.0797

Gnomad SAS AF: 0.0241

Gnomad FIN AF: 0.00621

Gnomad MID AF: 0.0278

Gnomad NFE AF: 0.0181

Gnomad OTH AF: 0.0239

GnomAD3 exomes AF: 0.267 AC: 51655 AN: 193734 Hom.: 10600 AF XY: 0.272 AC XY: 28944 AN XY: 106472

Gnomad AFR exome AF: 0.154

Gnomad AMR exome AF: 0.388

Gnomad ASJ exome AF: 0.196

Gnomad EAS exome AF: 0.479

Gnomad SAS exome AF: 0.345

Gnomad FIN exome AF: 0.180

Gnomad NFE exome AF: 0.225

Gnomad OTH exome AF: 0.221

GnomAD4 exome Data not reliable, filtered out with message: AS_VQSR AF: 0.239 AC: 288026 AN: 1202724 Hom.: 50997 Cov.: 28 AF XY: 0.233 AC XY: 139154 AN XY: 596090

Gnomad4 AFR exome AF: 0.172

Gnomad4 AMR exome AF: 0.395

Gnomad4 ASJ exome AF: 0.146

Gnomad4 EAS exome AF: 0.285

Gnomad4 SAS exome AF: 0.242

Gnomad4 FIN exome AF: 0.0948

Gnomad4 NFE exome AF: 0.245

Gnomad4 OTH exome AF: 0.208

GnomAD4 genome Data not reliable, filtered out with message: AS_VQSR AF: 0.0165 AC: 1084 AN: 65648 Hom.: 4 Cov.: 9 AF XY: 0.0151 AC XY: 471 AN XY: 31148

Gnomad4 AFR AF: 0.00935

Gnomad4 AMR AF: 0.0243

Gnomad4 ASJ AF: 0.00806

Gnomad4 EAS AF: 0.0787

Gnomad4 SAS AF: 0.0241

Gnomad4 FIN AF: 0.00621

Gnomad4 NFE AF: 0.0181

Gnomad4 OTH AF: 0.0248

Alfa AF: 0.160 Hom.: 490

ExAC AF: 0.349 AC: 42050

ClinVar

Significance: Benign

Submissions summary: Benign:2

Revision: criteria provided, multiple submitters, no conflicts

Submissions by phenotype

not specified Benign:1

Benign, criteria provided, single submitter

clinical testing

Laboratory for Molecular Medicine, Mass General Brigham Personalized Medicine

Mar 28, 2016

Variant identified in a genome or exome case(s) and assessed due to predicted null impact of the variant or pathogenic assertions in the literature or databases. Disclaimer: This variant has not undergone full assessment. The following are preliminary notes: ExAC frequency -

not provided Benign:1

Benign, criteria provided, single submitter

not provided

Breakthrough Genomics, Breakthrough Genomics

-

- -

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
AlphaMissense	Benign	0.079
BayesDel_addAF	Benign	-0.38	T
BayesDel_noAF	Benign	-0.78
CADD	Benign	0.0010
DANN	Benign	0.46
DEOGEN2	Benign	0.0021	.;.;T;.;.;.;T
Eigen	Benign	-1.5
Eigen_PC	Benign	-1.7
FATHMM_MKL	Benign	0.00071	N
LIST_S2	Benign	0.14	.;.;T;T;T;T;T
MetaRNN	Benign	0.0054	T;T;T;T;T;T;T
MetaSVM	Benign	-1.0	T
MutationTaster	Benign	1.0	P;P;P;P;P;P;P;P
PrimateAI	Benign	0.26	T
PROVEAN	Benign	0.22	.;N;.;.;N;N;N
REVEL	Benign	0.010
Sift	Benign	0.58	.;T;.;.;T;T;T
Sift4G	Benign	0.22	.;T;T;T;T;T;.
Vest4		0.080, 0.082, 0.084, 0.032, 0.049
MPC		1.5
ClinPred		0.0052	T
GERP RS		-5.6
gMVP		0.21

Splicing

Name	Calibrated prediction	Score	Prediction
SpliceAI score (max)		0.010		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: rs2290834; hg19: chr1-161599571; COSMIC: COSV54209014; COSMIC: COSV54209014;