1-161629864-G-T

Variant summary

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

The NM_001244753.2(FCGR3B):c.233C>A(p.Ala78Asp) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0305 in 1,486,942 control chromosomes in the GnomAD database, including 4,465 homozygotes. In-silico tool predicts a benign outcome for this variant. 13/18 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 0.075 (1102 hom., cov: 10)
  • Exomes 𝑓: 0.028 (3363 hom.)
• Consequence: FCGR3B NM_001244753.2 missense
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -2.01

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=0.0067406297).
• BA1: GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.223 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
FCGR3B	NM_001244753.2	c.233C>A	p.Ala78Asp	missense_variant	3/5	ENST00000650385.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
FCGR3B	ENST00000650385.1	c.233C>A	p.Ala78Asp	missense_variant	3/5		NM_001244753.2	P2

Frequencies

GnomAD3 genomes AF: 0.0748 AC: 6124 AN: 81818 Hom.: 1102 Cov.: 10

Gnomad AFR AF: 0.229

Gnomad AMI AF: 0.0490

Gnomad AMR AF: 0.0386

Gnomad ASJ AF: 0.0218

Gnomad EAS AF: 0.00

Gnomad SAS AF: 0.119

Gnomad FIN AF: 0.0344

Gnomad MID AF: 0.0482

Gnomad NFE AF: 0.0292

Gnomad OTH AF: 0.0589

GnomAD3 exomes AF: 0.0378 AC: 9301 AN: 245862 Hom.: 971 AF XY: 0.0374 AC XY: 4990 AN XY: 133314

Gnomad AFR exome AF: 0.195

Gnomad AMR exome AF: 0.0194

Gnomad ASJ exome AF: 0.0238

Gnomad EAS exome AF: 0.000170

Gnomad SAS exome AF: 0.0756

Gnomad FIN exome AF: 0.0261

Gnomad NFE exome AF: 0.0216

Gnomad OTH exome AF: 0.0313

GnomAD4 exome AF: 0.0279 AC: 39227 AN: 1405084 Hom.: 3363 Cov.: 35 AF XY: 0.0294 AC XY: 20540 AN XY: 697870

Gnomad4 AFR exome AF: 0.207

Gnomad4 AMR exome AF: 0.0214

Gnomad4 ASJ exome AF: 0.0241

Gnomad4 EAS exome AF: 0.0000317

Gnomad4 SAS exome AF: 0.0847

Gnomad4 FIN exome AF: 0.0258

Gnomad4 NFE exome AF: 0.0197

Gnomad4 OTH exome AF: 0.0339

GnomAD4 genome AF: 0.0749 AC: 6131 AN: 81858 Hom.: 1102 Cov.: 10 AF XY: 0.0762 AC XY: 2931 AN XY: 38460

Gnomad4 AFR AF: 0.228

Gnomad4 AMR AF: 0.0386

Gnomad4 ASJ AF: 0.0218

Gnomad4 EAS AF: 0.00

Gnomad4 SAS AF: 0.120

Gnomad4 FIN AF: 0.0344

Gnomad4 NFE AF: 0.0291

Gnomad4 OTH AF: 0.0582

Alfa AF: 0.0147 Hom.: 22

ESP6500AA AF: 0.194 AC: 839

ESP6500EA AF: 0.0199 AC: 171

ExAC AF: 0.0418 AC: 5053

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
AlphaMissense	Benign	0.12
BayesDel_addAF	Benign	-0.60	T
BayesDel_noAF	Benign	-0.62
Cadd	Benign	0.019
Dann	Benign	0.60
Eigen	Benign	-1.4
Eigen_PC	Benign	-1.5
FATHMM_MKL	Benign	0.0047	N
MetaRNN	Benign	0.0067	T;T;T;T;T;T;T
MetaSVM	Benign	-0.94	T
MutationTaster	Benign	1.0	P;P;P;P;P;P;P;P
PrimateAI	Benign	0.31	T
Vest4		0.11, 0.14, 0.12, 0.087, 0.10
MPC		2.3
ClinPred		0.00048	T
GERP RS		-4.0
gMVP		0.20

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: rs5030738; hg19: chr1-161599654;