1-161629853-T-C

Position:

• chr1-161629853-T-C

Variant summary

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

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. 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 0.017 (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

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=0.0061926544).
• BA1: GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.0581 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
FCGR3B	NM_001244753.2	c.244A>G	p.Asn82Asp	missense_variant	3/5	ENST00000650385.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
FCGR3B	ENST00000650385.1	c.244A>G	p.Asn82Asp	missense_variant	3/5		NM_001244753.2	P2

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

GnomAD3 exomes AF: 0.101 AC: 19732 AN: 194850 Hom.: 8390 AF XY: 0.102 AC XY: 10800 AN XY: 106354

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 SAS exome AF: 0.145

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

Gnomad4 AFR exome AF: 0.196

Gnomad4 AMR exome AF: 0.288

Gnomad4 ASJ exome AF: 0.0701

Gnomad4 EAS exome AF: 0.329

Gnomad4 SAS exome AF: 0.201

Gnomad4 FIN exome AF: 0.0659

Gnomad4 NFE exome AF: 0.118

Gnomad4 OTH exome AF: 0.125

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

Gnomad4 AFR AF: 0.0180

Gnomad4 AMR AF: 0.0245

Gnomad4 ASJ AF: 0.0125

Gnomad4 EAS AF: 0.0703

Gnomad4 SAS AF: 0.0303

Gnomad4 FIN AF: 0.00397

Gnomad4 NFE AF: 0.0158

Gnomad4 OTH AF: 0.0204

Alfa AF: 0.140 Hom.: 703

ExAC AF: 0.138 AC: 16308

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

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;.;.;.;T
Eigen	Benign	-1.5
Eigen_PC	Benign	-1.6
FATHMM_MKL	Benign	0.0016	N
LIST_S2	Benign	0.33	.;.;T;T;T;T;T
MetaRNN	Benign	0.0062	T;T;T;T;T;T;T
MetaSVM	Benign	-0.98	T
MutationTaster	Benign	1.0	N;N;N;N;N;N;N;N
PrimateAI	Benign	0.30	T
PROVEAN	Benign	-1.6	.;N;.;.;N;N;N
REVEL	Benign	0.0070
Sift	Benign	0.15	.;T;.;.;T;T;T
Sift4G	Benign	0.22	.;T;T;T;T;T;.
Vest4		0.077, 0.10, 0.11, 0.068, 0.086
MPC		1.9
ClinPred		0.0076	T
GERP RS		-5.6
gMVP		0.17

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