rs1050501

Variant names:

• chr1-161674008-T-C
• rs1050501
• NM_001394477.1:c.695T>C

Your query was ambiguous. Multiple possible variants found:

• chr1-161674008-T-C
• chr1-161674008-T-A

Variant summary

Our verdict is Benign. The variant received -12 ACMG points: 0P and 12B. BP4_Strong BA1

The NM_001394477.1(FCGR2B):​c.695T>C​(p.Ile232Thr) variant causes a missense change involving the alteration of a non-conserved nucleotide. In-silico tool predicts a benign outcome for this variant. 15/21 in silico tools predict a benign outcome for this variant. Variant has been reported in ClinVar as protective,risk factor (no stars).

• Frequency:
  • Genomes: 𝑓 0.19 (1242 hom., cov: 10)
  • Exomes 𝑓: 0.14 (3989 hom.)
• Consequence: FCGR2B NM_001394477.1 missense
• Clinical Significance: protective; risk factor no assertion criteria provided B:1 O:1
• Conservation: PhyloP100: 0.740
• Publications: 189 publications found

Genes affected

FCGR2B (HGNC:3618): (Fc gamma receptor IIb) The protein encoded by this gene is a low affinity receptor for the Fc region of immunoglobulin gamma complexes. The encoded protein is involved in the phagocytosis of immune complexes and in the regulation of antibody production by B-cells. Variations in this gene may increase susceptibilty to systemic lupus erythematosus (SLE). Several transcript variants encoding different isoforms have been found for this gene. [provided by RefSeq, Jun 2010]

FCGR2B Gene-Disease associations (from GenCC):

• systemic lupus erythematosus

  Inheritance: Unknown Classification: SUPPORTIVE, NO_KNOWN Submitted by: Orphanet, Labcorp Genetics (formerly Invitae)

ENSG00000234211 (HGNC:):

ACMG classification

Our verdict: Benign. The variant received -12 ACMG points.

• BP4: Computational evidence support a benign effect (MetaRNN=0.005741954).
• BA1: GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.27 is higher than 0.05.

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_001394477.1. 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
	FCGR2B	NM_001394477.1	MANE Select	c.695T>C	p.Ile232Thr	missense	Exon 5 of 8	NP_001381406.1	P31994-1
	FCGR2B	NM_004001.5		c.695T>C	p.Ile232Thr	missense	Exon 6 of 9	NP_003992.3
	FCGR2B	NM_001002275.3		c.692T>C	p.Ile231Thr	missense	Exon 6 of 9	NP_001002275.1	P31994-4

Ensembl Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	FCGR2B	ENST00000358671.10	TSL:1 MANE Select	c.695T>C	p.Ile232Thr	missense	Exon 5 of 8	ENSP00000351497.5	P31994-1
	FCGR2B	ENST00000367961.8	TSL:1	c.674T>C	p.Ile225Thr	missense	Exon 4 of 7	ENSP00000356938.4	P31994-3
	FCGR2B	ENST00000236937.13	TSL:1	c.695T>C	p.Ile232Thr	missense	Exon 5 of 7	ENSP00000236937.9	P31994-2

Frequencies

GnomAD3 genomes AF: 0.189 AC: 14950 AN: 78916 Hom.: 1237 Cov.: 10

Gnomad AFR AF: 0.276

Gnomad AMI AF: 0.0651

Gnomad AMR AF: 0.150

Gnomad ASJ AF: 0.134

Gnomad EAS AF: 0.270

Gnomad SAS AF: 0.164

Gnomad FIN AF: 0.252

Gnomad MID AF: 0.118

Gnomad NFE AF: 0.135

Gnomad OTH AF: 0.183

GnomAD2 exomes AF: 0.161 AC: 11190 AN: 69660 AF XY: 0.159

Gnomad AFR exome AF: 0.254

Gnomad AMR exome AF: 0.0993

Gnomad ASJ exome AF: 0.123

Gnomad EAS exome AF: 0.240

Gnomad FIN exome AF: 0.248

Gnomad NFE exome AF: 0.122

Gnomad OTH exome AF: 0.142

GnomAD4 exome AF: 0.141 AC: 62003 AN: 438644 Hom.: 3989 Cov.: 5 AF XY: 0.141 AC XY: 32409 AN XY: 230286

African (AFR) AF: 0.248 AC: 3166 AN: 12762

American (AMR) AF: 0.101 AC: 1774 AN: 17608

Ashkenazi Jewish (ASJ) AF: 0.128 AC: 1676 AN: 13112

East Asian (EAS) AF: 0.237 AC: 6935 AN: 29260

South Asian (SAS) AF: 0.132 AC: 5990 AN: 45284

European-Finnish (FIN) AF: 0.205 AC: 7491 AN: 36606

Middle Eastern (MID) AF: 0.129 AC: 237 AN: 1834

European-Non Finnish (NFE) AF: 0.121 AC: 31147 AN: 257642

Other (OTH) AF: 0.146 AC: 3587 AN: 24536

GnomAD4 genome AF: 0.190 AC: 14975 AN: 78964 Hom.: 1242 Cov.: 10 AF XY: 0.194 AC XY: 6879 AN XY: 35370

African (AFR) AF: 0.276 AC: 6579 AN: 23846

American (AMR) AF: 0.150 AC: 843 AN: 5622

Ashkenazi Jewish (ASJ) AF: 0.134 AC: 298 AN: 2220

East Asian (EAS) AF: 0.271 AC: 860 AN: 3176

South Asian (SAS) AF: 0.164 AC: 315 AN: 1922

European-Finnish (FIN) AF: 0.252 AC: 852 AN: 3386

Middle Eastern (MID) AF: 0.118 AC: 25 AN: 212

European-Non Finnish (NFE) AF: 0.135 AC: 4976 AN: 36936

Other (OTH) AF: 0.182 AC: 187 AN: 1030

Alfa AF: 0.151 Hom.: 553

ExAC AF: 0.107 AC: 6193

ClinVar

ClinVar submissions

Significance: protective; risk factor

Revision: no assertion criteria provided

Pathogenic	VUS	Benign	Condition
-	-	-	Malaria, resistance to (1)
-	-	-	Systemic lupus erythematosus, susceptibility to (1)

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
AlphaMissense	Benign	0.12
BayesDel_addAF	Benign	-0.63	T
BayesDel_noAF	Benign	-0.54
CADD	Benign	11
DANN	Benign	0.89
DEOGEN2	Benign	0.047	T
Eigen	Benign	-0.75
Eigen_PC	Benign	-0.76
FATHMM_MKL	Benign	0.043	N
LIST_S2	Benign	0.68	T
MetaRNN	Benign	0.0057	T
MetaSVM	Benign	-1.0	T
MutationAssessor	Benign	1.0	L
PhyloP100		0.74
PrimateAI	Benign	0.41	T
PROVEAN	Benign	-1.9	N
REVEL	Benign	0.024
Sift	Benign	0.22	T
Sift4G	Benign	0.17	T
Polyphen		0.10	B
Vest4		0.10
MPC		0.95
ClinPred		0.0034	T
GERP RS		2.9
Varity_R		0.029
gMVP		0.24
Mutation Taster		=100/0	polymorphism (auto)

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: rs1050501; hg19: chr1-161643798; COSMIC: COSV52680659;