chr1-161626224-A-G

Position:

• chr1-161626224-A-G

Variant summary

Our verdict is Benign. Variant got -13 ACMG points: 0P and 13B. BP4_Strong BP7 BA1

The NM_001244753.2(FCGR3B):​c.498T>C​(p.Asp166=) variant causes a synonymous change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00384 in 1,557,940 control chromosomes in the GnomAD database, including 497 homozygotes. In-silico tool predicts a benign outcome for this variant. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar.

• Frequency:
  • Genomes: 𝑓 0.018 (216 hom., cov: 28)
  • Exomes 𝑓: 0.0024 (281 hom.)
• Consequence: FCGR3B NM_001244753.2 synonymous
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 2.94

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 -13 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.96).
• BP7: Synonymous conserved (PhyloP=2.94 with no splicing effect.
• BA1: GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.0613 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
FCGR3B	NM_001244753.2	c.498T>C	p.Asp166=	synonymous_variant	4/5	ENST00000650385.1	NP_001231682.2

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
FCGR3B	ENST00000650385.1	c.498T>C	p.Asp166=	synonymous_variant	4/5		NM_001244753.2	ENSP00000497461	P2

Frequencies

GnomAD3 genomes AF: 0.0181 AC: 2676 AN: 147846 Hom.: 216 Cov.: 28

Gnomad AFR AF: 0.0636

Gnomad AMI AF: 0.00

Gnomad AMR AF: 0.00442

Gnomad ASJ AF: 0.000294

Gnomad EAS AF: 0.000194

Gnomad SAS AF: 0.000647

Gnomad FIN AF: 0.000195

Gnomad MID AF: 0.00

Gnomad NFE AF: 0.000451

Gnomad OTH AF: 0.0153

GnomAD3 exomes AF: 0.00484 AC: 1196 AN: 247204 Hom.: 130 AF XY: 0.00356 AC XY: 475 AN XY: 133544

Gnomad AFR exome AF: 0.0651

Gnomad AMR exome AF: 0.00249

Gnomad ASJ exome AF: 0.000101

Gnomad EAS exome AF: 0.000383

Gnomad SAS exome AF: 0.000569

Gnomad FIN exome AF: 0.000140

Gnomad NFE exome AF: 0.000314

Gnomad OTH exome AF: 0.00200

GnomAD4 exome AF: 0.00235 AC: 3314 AN: 1409978 Hom.: 281 Cov.: 33 AF XY: 0.00208 AC XY: 1460 AN XY: 702606

Gnomad4 AFR exome AF: 0.0690

Gnomad4 AMR exome AF: 0.00274

Gnomad4 ASJ exome AF: 0.0000393

Gnomad4 EAS exome AF: 0.000405

Gnomad4 SAS exome AF: 0.000855

Gnomad4 FIN exome AF: 0.000132

Gnomad4 NFE exome AF: 0.000562

Gnomad4 OTH exome AF: 0.00397

GnomAD4 genome AF: 0.0181 AC: 2673 AN: 147962 Hom.: 216 Cov.: 28 AF XY: 0.0171 AC XY: 1234 AN XY: 72262

Gnomad4 AFR AF: 0.0633

Gnomad4 AMR AF: 0.00442

Gnomad4 ASJ AF: 0.000294

Gnomad4 EAS AF: 0.000195

Gnomad4 SAS AF: 0.000647

Gnomad4 FIN AF: 0.000195

Gnomad4 NFE AF: 0.000451

Gnomad4 OTH AF: 0.0152

Alfa AF: 0.00752 Hom.: 26

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.96
CADD	Benign	3.9
DANN	Benign	0.69

Splicing

Name	Calibrated prediction	Score	Prediction
SpliceAI score (max)		0.030		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: rs71632957; hg19: chr1-161596014; COSMIC: COSV54212046; COSMIC: COSV54212046;