NM_001244753.2:c.233C>A

Variant names:

• chr1-161629864-G-T
• rs5030738
• NM_001244753.2:c.233C>A

Variant summary

Our verdict is Benign. The variant received -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. 14/19 in silico tools predict a benign outcome for this variant. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar.

• 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
• Publications: 27 publications found

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]

FCGR3B Gene-Disease associations (from GenCC):

• systemic lupus erythematosus

  Inheritance: Unknown Classification: SUPPORTIVE Submitted by: Orphanet

ENSG00000289768 (HGNC:):

ACMG classification

Our verdict: Benign. The variant received -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.

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_001244753.2. You can select a different transcript below to see updated ACMG assignments.

RefSeq Transcripts

Selected	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	FCGR3B	NM_001244753.2	MANE Select	c.233C>A	p.Ala78Asp	missense	Exon 3 of 5	NP_001231682.2
	FCGR3B	NM_000570.5		c.233C>A	p.Ala78Asp	missense	Exon 4 of 6	NP_000561.3
	FCGR3B	NM_001271035.2		c.230C>A	p.Ala77Asp	missense	Exon 3 of 5	NP_001257964.2

Ensembl Transcripts

Selected	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	FCGR3B	ENST00000650385.1	MANE Select	c.233C>A	p.Ala78Asp	missense	Exon 3 of 5	ENSP00000497461.1
	ENSG00000289768	ENST00000699402.1		c.40+1191C>A		intron	N/A	ENSP00000514363.1
	FCGR3B	ENST00000367964.6	TSL:5	c.233C>A	p.Ala78Asp	missense	Exon 4 of 6	ENSP00000356941.2

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

GnomAD2 exomes AF: 0.0378 AC: 9301 AN: 245862 AF XY: 0.0374

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 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

African (AFR) AF: 0.207 AC: 6172 AN: 29748

American (AMR) AF: 0.0214 AC: 902 AN: 42126

Ashkenazi Jewish (ASJ) AF: 0.0241 AC: 608 AN: 25194

East Asian (EAS) AF: 0.0000317 AC: 1 AN: 31540

South Asian (SAS) AF: 0.0847 AC: 6843 AN: 80818

European-Finnish (FIN) AF: 0.0258 AC: 1278 AN: 49464

Middle Eastern (MID) AF: 0.0342 AC: 186 AN: 5440

European-Non Finnish (NFE) AF: 0.0197 AC: 21304 AN: 1083652

Other (OTH) AF: 0.0339 AC: 1933 AN: 57102

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

African (AFR) AF: 0.228 AC: 4039 AN: 17684

American (AMR) AF: 0.0386 AC: 247 AN: 6402

Ashkenazi Jewish (ASJ) AF: 0.0218 AC: 56 AN: 2574

East Asian (EAS) AF: 0.00 AC: 0 AN: 1874

South Asian (SAS) AF: 0.120 AC: 216 AN: 1804

European-Finnish (FIN) AF: 0.0344 AC: 173 AN: 5032

Middle Eastern (MID) AF: 0.0467 AC: 10 AN: 214

European-Non Finnish (NFE) AF: 0.0291 AC: 1303 AN: 44702

Other (OTH) AF: 0.0582 AC: 63 AN: 1082

Alfa AF: 0.0228 Hom.: 185

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 v4.9

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
DEOGEN2	Benign	0.020	T
Eigen	Benign	-1.4
Eigen_PC	Benign	-1.5
FATHMM_MKL	Benign	0.0047	N
LIST_S2	Benign	0.21	T
MetaRNN	Benign	0.0067	T
MetaSVM	Benign	-0.94	T
PhyloP100		-2.0
PrimateAI	Benign	0.31	T
PROVEAN	Benign	-0.84	N
REVEL	Benign	0.023
Sift	Benign	0.34	T
Sift4G	Benign	0.48	T
Vest4		0.11
MPC		2.3
ClinPred		0.00048	T
GERP RS		-4.0
gMVP		0.20
Mutation Taster		=97/3	polymorphism (auto)

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

Other links and lift over

dbSNP: rs5030738; hg19: chr1-161599654;