rs200303549

Variant names:

• chr1-161629785-G-T
• rs200303549
• NM_001244753.2:c.312C>A

Variant summary

Our verdict is Benign. The variant received -9 ACMG points: 0P and 9B. BP4_Moderate BP6_Moderate BP7 BS2

The NM_001244753.2(FCGR3B):​c.312C>A​(p.Val104Val) variant causes a synonymous change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0103 in 1,431,338 control chromosomes in the GnomAD database, including 1,573 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★).

• Frequency:
  • Genomes: 𝑓 0.011 (93 hom., cov: 10)
  • Exomes 𝑓: 0.010 (1480 hom.)
• Consequence: FCGR3B NM_001244753.2 synonymous
• Clinical Significance: Benign criteria provided, single submitter B:1
• Conservation: PhyloP100: 0.273
• Publications: 3 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 -9 ACMG points.

• BP4: Computational evidence support a benign effect (REVEL=0.05).
• BP6: Variant 1-161629785-G-T is Benign according to our data. Variant chr1-161629785-G-T is described in ClinVar as Benign. ClinVar VariationId is 2639515.Status of the report is criteria_provided_single_submitter, 1 stars.
• BP7: Synonymous conserved (PhyloP=0.273 with no splicing effect.
• BS2: High Homozygotes in GnomAd4 at 93 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

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	FCGR3B	NM_001244753.2	MANE Select	c.312C>A	p.Val104Val	synonymous	Exon 3 of 5	NP_001231682.2	A0A3B3ISU3
	FCGR3B	NM_000570.5		c.312C>A	p.Val104Val	synonymous	Exon 4 of 6	NP_000561.3	O75015
	FCGR3B	NM_001271035.2		c.309C>A	p.Val103Val	synonymous	Exon 3 of 5	NP_001257964.2	H0Y4U3

Ensembl Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	FCGR3B	ENST00000650385.1	MANE Select	c.312C>A	p.Val104Val	synonymous	Exon 3 of 5	ENSP00000497461.1	A0A3B3ISU3
	ENSG00000289768	ENST00000699402.1		c.40+1270C>A		intron	N/A	ENSP00000514363.1	A0A8V8TN80
	FCGR3B	ENST00000367964.6	TSL:5	c.312C>A	p.Val104Val	synonymous	Exon 4 of 6	ENSP00000356941.2	O75015

Frequencies

GnomAD3 genomes AF: 0.0108 AC: 834 AN: 76938 Hom.: 93 Cov.: 10

Gnomad AFR AF: 0.00291

Gnomad AMI AF: 0.0372

Gnomad AMR AF: 0.00859

Gnomad ASJ AF: 0.00207

Gnomad EAS AF: 0.00

Gnomad SAS AF: 0.00363

Gnomad FIN AF: 0.0379

Gnomad MID AF: 0.00450

Gnomad NFE AF: 0.0124

Gnomad OTH AF: 0.0102

GnomAD2 exomes AF: 0.00920 AC: 2108 AN: 229208 AF XY: 0.00922

Gnomad AFR exome AF: 0.00177

Gnomad AMR exome AF: 0.00357

Gnomad ASJ exome AF: 0.00102

Gnomad EAS exome AF: 0.00

Gnomad FIN exome AF: 0.0325

Gnomad NFE exome AF: 0.0111

Gnomad OTH exome AF: 0.00739

GnomAD4 exome AF: 0.0103 AC: 13944 AN: 1354350 Hom.: 1480 Cov.: 30 AF XY: 0.0102 AC XY: 6825 AN XY: 672076

African (AFR) AF: 0.00150 AC: 42 AN: 27950

American (AMR) AF: 0.00410 AC: 166 AN: 40498

Ashkenazi Jewish (ASJ) AF: 0.00128 AC: 32 AN: 24906

East Asian (EAS) AF: 0.0000347 AC: 1 AN: 28852

South Asian (SAS) AF: 0.00440 AC: 331 AN: 75222

European-Finnish (FIN) AF: 0.0320 AC: 1519 AN: 47432

Middle Eastern (MID) AF: 0.00267 AC: 14 AN: 5242

European-Non Finnish (NFE) AF: 0.0109 AC: 11407 AN: 1049238

Other (OTH) AF: 0.00785 AC: 432 AN: 55010

GnomAD4 genome AF: 0.0108 AC: 832 AN: 76988 Hom.: 93 Cov.: 10 AF XY: 0.0112 AC XY: 404 AN XY: 36116

African (AFR) AF: 0.00290 AC: 52 AN: 17958

American (AMR) AF: 0.00842 AC: 49 AN: 5822

Ashkenazi Jewish (ASJ) AF: 0.00207 AC: 5 AN: 2418

East Asian (EAS) AF: 0.00 AC: 0 AN: 1612

South Asian (SAS) AF: 0.00302 AC: 5 AN: 1654

European-Finnish (FIN) AF: 0.0379 AC: 183 AN: 4834

Middle Eastern (MID) AF: 0.00485 AC: 1 AN: 206

European-Non Finnish (NFE) AF: 0.0124 AC: 511 AN: 41060

Other (OTH) AF: 0.0101 AC: 10 AN: 994

Alfa AF: 0.00611 Hom.: 14

ClinVar

ClinVar submissions

Significance: Benign

Revision: criteria provided, single submitter

Pathogenic	VUS	Benign	Condition
-	-	1	not provided (1)

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.94
CADD	Benign	6.9
DANN	Benign	0.72
PhyloP100		0.27
Mutation Taster		=100/0	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: rs200303549; hg19: chr1-161599575;