rs5030738

Positions:

• chr1-161629864-G-A
• chr1-161629864-G-T

Variant summary

Our verdict is Uncertain significance. Variant got 0 ACMG points: 2P and 2B. PM2 BP4_Moderate

The NM_001244753.2(FCGR3B):​c.233C>T​(p.Ala78Val) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0000135 in 1,405,640 control chromosomes in the GnomAD database, including 1 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. Another variant affecting the same amino acid position, but resulting in a different missense (i.e. A78D) has been classified as Likely benign.

• Frequency:
  • Genomes: not found (cov: 10)
  • Exomes 𝑓: 0.000014 (1 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 Uncertain_significance. Variant got 0 ACMG points.

• PM2: Very rare variant in population databases, with high coverage
• BP4: Computational evidence support a benign effect (MetaRNN=0.16208252).

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
FCGR3B	NM_001244753.2	c.233C>T	p.Ala78Val	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.233C>T	p.Ala78Val	missense_variant	3/5		NM_001244753.2	ENSP00000497461	P2

Frequencies

GnomAD3 genomes Cov.: 10

GnomAD4 exome AF: 0.0000135 AC: 19 AN: 1405640 Hom.: 1 Cov.: 35 AF XY: 0.0000143 AC XY: 10 AN XY: 698118

Gnomad4 AFR exome AF: 0.00

Gnomad4 AMR exome AF: 0.00

Gnomad4 ASJ exome AF: 0.00

Gnomad4 EAS exome AF: 0.00

Gnomad4 SAS exome AF: 0.00

Gnomad4 FIN exome AF: 0.00

Gnomad4 NFE exome AF: 0.0000148

Gnomad4 OTH exome AF: 0.0000350

GnomAD4 genome Cov.: 10

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
AlphaMissense	Benign	0.15
BayesDel_addAF	Benign	-0.30	T
BayesDel_noAF	Benign	-0.66
CADD	Benign	0.059
DANN	Benign	0.95
DEOGEN2	Benign	0.030	.;.;T;.;.;.;T
Eigen	Benign	-1.0
Eigen_PC	Benign	-1.3
FATHMM_MKL	Benign	0.0065	N
LIST_S2	Benign	0.30	.;.;T;T;T;T;T
M_CAP	Benign	0.0016	T
MetaRNN	Benign	0.16	T;T;T;T;T;T;T
MetaSVM	Benign	-0.99	T
MutationTaster	Benign	1.0	N;N;N;N;N;N;N;N
PrimateAI	Benign	0.29	T
PROVEAN	Benign	-2.1	.;N;.;.;N;N;N
REVEL	Benign	0.039
Sift	Benign	0.13	.;T;.;.;T;T;T
Sift4G	Benign	0.18	.;T;T;T;T;T;.
Vest4		0.11, 0.11, 0.11, 0.10, 0.094
MutPred		0.36		Loss of loop (P = 0.1242);Loss of loop (P = 0.1242);.;.;Loss of loop (P = 0.1242);.;.;
MVP		0.13
MPC		1.7
ClinPred		0.15	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;