NM_001244753.2:c.108C>T

Variant names:

• chr1-161629989-G-A
• rs200688856
• NM_001244753.2:c.108C>T

Variant summary

Our verdict is Benign. The variant received -7 ACMG points: 0P and 7B. BP4_Moderate BP7 BS2

The NM_001244753.2(FCGR3B):​c.108C>T​(p.Ser36Ser) variant causes a synonymous change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0000279 in 1,363,282 control chromosomes in the GnomAD database, including 10 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 0.000046 (1 hom., cov: 17)
  • Exomes 𝑓: 0.000026 (9 hom.)
• Consequence: FCGR3B NM_001244753.2 synonymous
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -1.01
• Publications: 21 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 -7 ACMG points.

• BP4: Computational evidence support a benign effect (REVEL=0.045).
• BP7: Synonymous conserved (PhyloP=-1.01 with no splicing effect.
• BS2: High Homozygotes in GnomAdExome4 at 9 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.108C>T	p.Ser36Ser	synonymous	Exon 3 of 5	NP_001231682.2
	FCGR3B	NM_000570.5		c.108C>T	p.Ser36Ser	synonymous	Exon 4 of 6	NP_000561.3
	FCGR3B	NM_001271035.2		c.105C>T	p.Ser35Ser	synonymous	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.108C>T	p.Ser36Ser	synonymous	Exon 3 of 5	ENSP00000497461.1
	ENSG00000289768	ENST00000699402.1		c.40+1066C>T		intron	N/A	ENSP00000514363.1
	FCGR3B	ENST00000367964.6	TSL:5	c.108C>T	p.Ser36Ser	synonymous	Exon 4 of 6	ENSP00000356941.2

Frequencies

GnomAD3 genomes AF: 0.0000462 AC: 5 AN: 108250 Hom.: 1 Cov.: 17

Gnomad AFR AF: 0.00

Gnomad AMI AF: 0.00

Gnomad AMR AF: 0.00

Gnomad ASJ AF: 0.00

Gnomad EAS AF: 0.00

Gnomad SAS AF: 0.00

Gnomad FIN AF: 0.00

Gnomad MID AF: 0.00

Gnomad NFE AF: 0.0000940

Gnomad OTH AF: 0.00

GnomAD2 exomes AF: 0.0000432 AC: 9 AN: 208406 AF XY: 0.0000442

Gnomad AFR exome AF: 0.00

Gnomad AMR exome AF: 0.00

Gnomad ASJ exome AF: 0.00

Gnomad EAS exome AF: 0.00

Gnomad FIN exome AF: 0.00

Gnomad NFE exome AF: 0.0000500

Gnomad OTH exome AF: 0.00

GnomAD4 exome AF: 0.0000263 AC: 33 AN: 1255032 Hom.: 9 Cov.: 33 AF XY: 0.0000273 AC XY: 17 AN XY: 623504

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

African (AFR) AF: 0.00 AC: 0 AN: 25938

American (AMR) AF: 0.00 AC: 0 AN: 34302

Ashkenazi Jewish (ASJ) AF: 0.00 AC: 0 AN: 23846

East Asian (EAS) AF: 0.00 AC: 0 AN: 24980

South Asian (SAS) AF: 0.0000735 AC: 5 AN: 68040

European-Finnish (FIN) AF: 0.0000220 AC: 1 AN: 45538

Middle Eastern (MID) AF: 0.000199 AC: 1 AN: 5022

European-Non Finnish (NFE) AF: 0.0000246 AC: 24 AN: 976126

Other (OTH) AF: 0.0000390 AC: 2 AN: 51240

⚠️ The allele balance in gnomAD4 Exomes is highly skewed from 0.5 (p-value = 0.0000000000302712), which strongly suggests a high chance of mosaicism in these individuals.

GnomAD4 genome AF: 0.0000462 AC: 5 AN: 108250 Hom.: 1 Cov.: 17 AF XY: 0.0000383 AC XY: 2 AN XY: 52158

African (AFR) AF: 0.00 AC: 0 AN: 27146

American (AMR) AF: 0.00 AC: 0 AN: 9612

Ashkenazi Jewish (ASJ) AF: 0.00 AC: 0 AN: 2922

East Asian (EAS) AF: 0.00 AC: 0 AN: 2420

South Asian (SAS) AF: 0.00 AC: 0 AN: 2836

European-Finnish (FIN) AF: 0.00 AC: 0 AN: 7808

Middle Eastern (MID) AF: 0.00 AC: 0 AN: 248

European-Non Finnish (NFE) AF: 0.0000940 AC: 5 AN: 53186

Other (OTH) AF: 0.00 AC: 0 AN: 1468

Alfa AF: 0.00 Hom.: 85

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.93
CADD	Benign	5.1
DANN	Benign	0.82
PhyloP100		-1.0
Mutation Taster		=100/0	polymorphism

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

Other links and lift over

dbSNP: rs200688856; hg19: chr1-161599779;