chr1-161629853-T-A

Variant names:

• chr1-161629853-T-A
• rs147574249
• NM_001244753.2:c.244A>T

Variant summary

Our verdict is Uncertain significance. The variant received 0 ACMG points: 2P and 2B. PM1 BP4_Moderate

The NM_001244753.2(FCGR3B):​c.244A>T​(p.Asn82Tyr) variant causes a missense change involving the alteration of a non-conserved nucleotide. In-silico tool predicts a benign outcome for this variant. 14/20 in silico tools predict a benign outcome for this variant. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar.

• Frequency:
  • Genomes: 𝑓 0.0 (0 hom., cov: 9)
  • Exomes 𝑓: 0.0000033 (0 hom.)
  • Failed GnomAD Quality Control
• Consequence: FCGR3B NM_001244753.2 missense
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -3.29
• Publications: 30 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: Uncertain_significance. The variant received 0 ACMG points.

• PM1: In a glycosylation_site N-linked (GlcNAc...) asparagine (size 0) in uniprot entity FCG3B_HUMAN
• BP4: Computational evidence support a benign effect (MetaRNN=0.1304524).

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.244A>T	p.Asn82Tyr	missense	Exon 3 of 5	NP_001231682.2
	FCGR3B	NM_000570.5		c.244A>T	p.Asn82Tyr	missense	Exon 4 of 6	NP_000561.3
	FCGR3B	NM_001271035.2		c.241A>T	p.Asn81Tyr	missense	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.244A>T	p.Asn82Tyr	missense	Exon 3 of 5	ENSP00000497461.1
	ENSG00000289768	ENST00000699402.1		c.40+1202A>T		intron	N/A	ENSP00000514363.1
	FCGR3B	ENST00000367964.6	TSL:5	c.244A>T	p.Asn82Tyr	missense	Exon 4 of 6	ENSP00000356941.2

Frequencies

GnomAD3 genomes AF: 0.00 AC: 0 AN: 68966 Hom.: 0 Cov.: 9

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: 0.00

Gnomad OTH AF: 0.00

GnomAD2 exomes AF: 0.0000205 AC: 4 AN: 194850 AF XY: 0.0000188

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: 0.0000553

Gnomad NFE exome AF: 0.0000324

Gnomad OTH exome AF: 0.00

GnomAD4 exome Data not reliable, filtered out with message: AS_VQSR AF: 0.00000333 AC: 4 AN: 1200492 Hom.: 0 Cov.: 31 AF XY: 0.00000334 AC XY: 2 AN XY: 598244

⚠️ 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: 25234

American (AMR) AF: 0.00 AC: 0 AN: 35114

Ashkenazi Jewish (ASJ) AF: 0.00 AC: 0 AN: 22284

East Asian (EAS) AF: 0.00 AC: 0 AN: 26088

South Asian (SAS) AF: 0.0000284 AC: 2 AN: 70472

European-Finnish (FIN) AF: 0.0000471 AC: 2 AN: 42420

Middle Eastern (MID) AF: 0.00 AC: 0 AN: 4562

European-Non Finnish (NFE) AF: 0.00 AC: 0 AN: 925746

Other (OTH) AF: 0.00 AC: 0 AN: 48572

⚠️ The allele balance in gnomAD4 Exomes is highly skewed from 0.5 (p-value = 0), which strongly suggests a high chance of mosaicism in these individuals.

GnomAD4 genome Data not reliable, filtered out with message: AC0;AS_VQSR AF: 0.00 AC: 0 AN: 68966 Hom.: 0 Cov.: 9 AF XY: 0.00 AC XY: 0 AN XY: 32612

African (AFR) AF: 0.00 AC: 0 AN: 15560

American (AMR) AF: 0.00 AC: 0 AN: 5282

Ashkenazi Jewish (ASJ) AF: 0.00 AC: 0 AN: 2198

East Asian (EAS) AF: 0.00 AC: 0 AN: 1246

South Asian (SAS) AF: 0.00 AC: 0 AN: 1500

European-Finnish (FIN) AF: 0.00 AC: 0 AN: 4564

Middle Eastern (MID) AF: 0.00 AC: 0 AN: 178

European-Non Finnish (NFE) AF: 0.00 AC: 0 AN: 37192

Other (OTH) AF: 0.00 AC: 0 AN: 894

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
AlphaMissense	Benign	0.12
BayesDel_addAF	Benign	-0.25	T
BayesDel_noAF	Benign	-0.59
CADD	Benign	0.018
DANN	Benign	0.97
DEOGEN2	Benign	0.086	T
Eigen	Benign	-1.3
Eigen_PC	Benign	-1.5
FATHMM_MKL	Benign	0.0053	N
LIST_S2	Benign	0.39	T
M_CAP	Benign	0.0021	T
MetaRNN	Benign	0.13	T
MetaSVM	Benign	-1.0	T
PhyloP100		-3.3
PrimateAI	Benign	0.30	T
PROVEAN	Uncertain	-4.4	D
REVEL	Benign	0.060
Sift	Uncertain	0.019	D
Sift4G	Uncertain	0.010	D
Vest4		0.26
MutPred		0.33		Loss of disorder (P = 0.1066)
MVP		0.12
MPC		2.0
ClinPred		0.077	T
GERP RS		-5.6
gMVP		0.28
Mutation Taster		=90/10	polymorphism

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

Other links and lift over

dbSNP: rs147574249; hg19: chr1-161599643;