chr1-161673191-C-T

Variant names:

• chr1-161673191-C-T
• rs137950262
• NM_001394477.1:c.608C>T

Variant summary

Our verdict is Likely benign. The variant received -6 ACMG points: 0P and 6B. BP4_Strong BP6_Moderate

The NM_001394477.1(FCGR2B):​c.608C>T​(p.Thr203Met) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.000873 in 150,048 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a benign outcome for this variant. 16/22 in silico tools predict a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★).

• Frequency:
  • Genomes: 𝑓 0.00087 (0 hom., cov: 32)
  • Exomes 𝑓: 0.0028 (0 hom.)
  • Failed GnomAD Quality Control
• Consequence: FCGR2B NM_001394477.1 missense
• Clinical Significance: Benign criteria provided, single submitter B:1
• Conservation: PhyloP100: -2.77
• Publications: 4 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: Likely_benign. The variant received -6 ACMG points.

• BP4: Computational evidence support a benign effect (MetaRNN=0.0041023493).
• BP6: Variant 1-161673191-C-T is Benign according to our data. Variant chr1-161673191-C-T is described in ClinVar as Benign. ClinVar VariationId is 2639516.Status of the report is criteria_provided_single_submitter, 1 stars.

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.608C>T	p.Thr203Met	missense	Exon 4 of 8	NP_001381406.1	P31994-1
	FCGR2B	NM_004001.5		c.608C>T	p.Thr203Met	missense	Exon 5 of 9	NP_003992.3
	FCGR2B	NM_001002275.3		c.605C>T	p.Thr202Met	missense	Exon 5 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.608C>T	p.Thr203Met	missense	Exon 4 of 8	ENSP00000351497.5	P31994-1
	FCGR2B	ENST00000367961.8	TSL:1	c.587C>T	p.Thr196Met	missense	Exon 3 of 7	ENSP00000356938.4	P31994-3
	FCGR2B	ENST00000236937.13	TSL:1	c.608C>T	p.Thr203Met	missense	Exon 4 of 7	ENSP00000236937.9	P31994-2

Frequencies

GnomAD3 genomes AF: 0.000874 AC: 131 AN: 149930 Hom.: 0 Cov.: 32

Gnomad AFR AF: 0.000197

Gnomad AMI AF: 0.00

Gnomad AMR AF: 0.000933

Gnomad ASJ AF: 0.000290

Gnomad EAS AF: 0.00290

Gnomad SAS AF: 0.000849

Gnomad FIN AF: 0.000961

Gnomad MID AF: 0.00

Gnomad NFE AF: 0.00116

Gnomad OTH AF: 0.000486

GnomAD2 exomes AF: 0.00237 AC: 585 AN: 246460 AF XY: 0.00254

Gnomad AFR exome AF: 0.000843

Gnomad AMR exome AF: 0.000907

Gnomad ASJ exome AF: 0.00141

Gnomad EAS exome AF: 0.00208

Gnomad FIN exome AF: 0.00432

Gnomad NFE exome AF: 0.00304

Gnomad OTH exome AF: 0.00217

GnomAD4 exome Data not reliable, filtered out with message: AS_VQSR AF: 0.00281 AC: 4068 AN: 1449216 Hom.: 0 Cov.: 30 AF XY: 0.00273 AC XY: 1968 AN XY: 720618

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

African (AFR) AF: 0.000391 AC: 13 AN: 33222

American (AMR) AF: 0.000564 AC: 25 AN: 44310

Ashkenazi Jewish (ASJ) AF: 0.00100 AC: 26 AN: 25958

East Asian (EAS) AF: 0.00237 AC: 94 AN: 39662

South Asian (SAS) AF: 0.000819 AC: 70 AN: 85510

European-Finnish (FIN) AF: 0.00229 AC: 121 AN: 52916

Middle Eastern (MID) AF: 0.000526 AC: 3 AN: 5706

European-Non Finnish (NFE) AF: 0.00327 AC: 3604 AN: 1101980

Other (OTH) AF: 0.00187 AC: 112 AN: 59952

⚠️ 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 AF: 0.000873 AC: 131 AN: 150048 Hom.: 0 Cov.: 32 AF XY: 0.000818 AC XY: 60 AN XY: 73334

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

African (AFR) AF: 0.000196 AC: 8 AN: 40794

American (AMR) AF: 0.000931 AC: 14 AN: 15030

Ashkenazi Jewish (ASJ) AF: 0.000290 AC: 1 AN: 3450

East Asian (EAS) AF: 0.00291 AC: 15 AN: 5152

South Asian (SAS) AF: 0.000850 AC: 4 AN: 4706

European-Finnish (FIN) AF: 0.000961 AC: 10 AN: 10408

Middle Eastern (MID) AF: 0.00 AC: 0 AN: 288

European-Non Finnish (NFE) AF: 0.00116 AC: 78 AN: 67232

Other (OTH) AF: 0.000481 AC: 1 AN: 2080

⚠️ The allele balance in gnomAD version 4 Genomes is significantly skewed from the expected value of 0.5. (p-value = 0), which strongly suggests a high chance of mosaicism in these individuals.

Alfa AF: 0.00186 Hom.: 0

ESP6500AA AF: 0.000912 AC: 4

ESP6500EA AF: 0.00431 AC: 37

ExAC AF: 0.00468 AC: 568

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
AlphaMissense	Benign	0.10
BayesDel_addAF	Benign	-0.32	T
BayesDel_noAF	Benign	-0.70
CADD	Benign	0.0010
DANN	Benign	0.40
DEOGEN2	Benign	0.038	T
Eigen	Benign	-1.5
Eigen_PC	Benign	-1.6
FATHMM_MKL	Benign	0.0030	N
LIST_S2	Benign	0.72	T
M_CAP	Benign	0.016	T
MetaRNN	Benign	0.0041	T
MetaSVM	Benign	-0.89	T
MutationAssessor	Benign	-0.18	N
PhyloP100		-2.8
PrimateAI	Benign	0.26	T
PROVEAN	Benign	-1.1	N
REVEL	Benign	0.046
Sift	Benign	0.36	T
Sift4G	Benign	0.58	T
Polyphen		0.38	B
Vest4		0.11
MVP		0.040
MPC		0.79
ClinPred		0.0079	T
GERP RS		-10
Varity_R		0.085
gMVP		0.27
Mutation Taster		=89/11	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: rs137950262; hg19: chr1-161642981; COSMIC: COSV99030787; COSMIC: COSV99030787;