1-161629853-T-C

Variant names:

• chr1-161629853-T-C
• rs147574249
• NM_001244753.2:c.244A>G

Variant summary

Our verdict is Likely benign. The variant received -6 ACMG points: 2P and 8B. PM1 BP4_Strong BS2

The NM_001244753.2(FCGR3B):​c.244A>G​(p.Asn82Asp) variant causes a missense change involving the alteration of a non-conserved nucleotide. 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 0.017 (4 hom., cov: 9)
  • Exomes 𝑓: 0.13 (52197 hom.)
  • Failed GnomAD Quality Control
• Consequence: FCGR3B NM_001244753.2 missense
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -3.29
• Publications: 30 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: Likely_benign. The variant received -6 ACMG points.

• PM1: In a glycosylation_site N-linked (GlcNAc...) asparagine (size 0) in uniprot entity FCG3B_HUMAN
• BP4: Computational evidence support a benign effect (MetaRNN=0.0061926544).
• BS2: High Homozygotes in GnomAd4 at 4 Unknown gene

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.244A>G	p.Asn82Asp	missense	Exon 3 of 5	NP_001231682.2
	FCGR3B	NM_000570.5		c.244A>G	p.Asn82Asp	missense	Exon 4 of 6	NP_000561.3
	FCGR3B	NM_001271035.2		c.241A>G	p.Asn81Asp	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.244A>G	p.Asn82Asp	missense	Exon 3 of 5	ENSP00000497461.1
	ENSG00000289768	ENST00000699402.1		c.40+1202A>G		intron	N/A	ENSP00000514363.1
	FCGR3B	ENST00000367964.6	TSL:5	c.244A>G	p.Asn82Asp	missense	Exon 4 of 6	ENSP00000356941.2

Frequencies

GnomAD3 genomes AF: 0.0175 AC: 1178 AN: 67356 Hom.: 4 Cov.: 9

Gnomad AFR AF: 0.0180

Gnomad AMI AF: 0.0329

Gnomad AMR AF: 0.0240

Gnomad ASJ AF: 0.0125

Gnomad EAS AF: 0.0709

Gnomad SAS AF: 0.0316

Gnomad FIN AF: 0.00397

Gnomad MID AF: 0.0114

Gnomad NFE AF: 0.0158

Gnomad OTH AF: 0.0216

GnomAD2 exomes AF: 0.101 AC: 19732 AN: 194850 AF XY: 0.102

Gnomad AFR exome AF: 0.150

Gnomad AMR exome AF: 0.154

Gnomad ASJ exome AF: 0.0501

Gnomad EAS exome AF: 0.316

Gnomad FIN exome AF: 0.0366

Gnomad NFE exome AF: 0.0611

Gnomad OTH exome AF: 0.0906

GnomAD4 exome Data not reliable, filtered out with message: AS_VQSR AF: 0.131 AC: 127311 AN: 970150 Hom.: 52197 Cov.: 31 AF XY: 0.133 AC XY: 64181 AN XY: 484064

⚠️ The allele balance in gnomAD version 4 Exomes is significantly skewed from the expected value of 0.5.

African (AFR) AF: 0.196 AC: 4063 AN: 20732

American (AMR) AF: 0.288 AC: 7822 AN: 27136

Ashkenazi Jewish (ASJ) AF: 0.0701 AC: 1304 AN: 18608

East Asian (EAS) AF: 0.329 AC: 6626 AN: 20116

South Asian (SAS) AF: 0.201 AC: 11878 AN: 58996

European-Finnish (FIN) AF: 0.0659 AC: 2495 AN: 37832

Middle Eastern (MID) AF: 0.0794 AC: 314 AN: 3954

European-Non Finnish (NFE) AF: 0.118 AC: 87878 AN: 743240

Other (OTH) AF: 0.125 AC: 4931 AN: 39536

⚠️ The allele balance in gnomAD4 Exomes is highly skewed from 0.5 (p-value = 0), which strongly suggests a high chance of mosaicism in these individuals.

GnomAD4 genome AF: 0.0175 AC: 1178 AN: 67380 Hom.: 4 Cov.: 9 AF XY: 0.0158 AC XY: 504 AN XY: 31994

⚠️ The allele balance in gnomAD version 4 Genomes is significantly skewed from the expected value of 0.5.

African (AFR) AF: 0.0180 AC: 274 AN: 15214

American (AMR) AF: 0.0245 AC: 126 AN: 5138

Ashkenazi Jewish (ASJ) AF: 0.0125 AC: 27 AN: 2156

East Asian (EAS) AF: 0.0703 AC: 83 AN: 1180

South Asian (SAS) AF: 0.0303 AC: 44 AN: 1454

European-Finnish (FIN) AF: 0.00397 AC: 18 AN: 4534

Middle Eastern (MID) AF: 0.0125 AC: 2 AN: 160

European-Non Finnish (NFE) AF: 0.0158 AC: 575 AN: 36326

Other (OTH) AF: 0.0204 AC: 18 AN: 884

⚠️ The allele balance in gnomAD version 4 Genomes is significantly skewed from the expected value of 0.5. (p-value = 0), which strongly suggests a high chance of mosaicism in these individuals.

Alfa AF: 0.140 Hom.: 703

ExAC AF: 0.138 AC: 16308

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
AlphaMissense	Benign	0.089
BayesDel_addAF	Benign	-0.78	T
BayesDel_noAF	Benign	-0.82
CADD	Benign	0.0020
DANN	Benign	0.76
DEOGEN2	Benign	0.028	T
Eigen	Benign	-1.5
Eigen_PC	Benign	-1.6
FATHMM_MKL	Benign	0.0016	N
LIST_S2	Benign	0.33	T
MetaRNN	Benign	0.0062	T
MetaSVM	Benign	-0.98	T
PhyloP100		-3.3
PrimateAI	Benign	0.30	T
PROVEAN	Benign	-1.6	N
REVEL	Benign	0.0070
Sift	Benign	0.15	T
Sift4G	Benign	0.22	T
Vest4		0.077
MPC		1.9
ClinPred		0.0076	T
GERP RS		-5.6
gMVP		0.17
Mutation Taster		=93/7	polymorphism (auto)

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

Other links and lift over

dbSNP: rs147574249; hg19: chr1-161599643; COSMIC: COSV54208798; COSMIC: COSV54208798;