1-161671493-A-T

Variant names:

• chr1-161671493-A-T
• rs780661874
• NM_001394477.1:c.235A>T

Variant summary

Our verdict is Uncertain significance. The variant received 0 ACMG points: 2P and 2B. PM2 BP4_Moderate

The NM_001394477.1(FCGR2B):​c.235A>T​(p.Ser79Cys) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant was absent in control chromosomes in GnomAD project. In-silico tool predicts a benign outcome for this variant. 15/22 in silico tools predict a benign outcome for this variant. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar. Another variant affecting the same amino acid position, but resulting in a different missense (i.e. S79G) has been classified as Uncertain significance.

• Frequency: Genomes: not found (cov: 29)
• Consequence: FCGR2B NM_001394477.1 missense
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -1.64
• Publications: 0 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)

ACMG classification

Our verdict: Uncertain_significance. The variant received 0 ACMG points.

• PM2: Very rare variant in population databases, with high coverage
• BP4: Computational evidence support a benign effect (MetaRNN=0.17213008).

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.235A>T	p.Ser79Cys	missense	Exon 3 of 8	NP_001381406.1	P31994-1
	FCGR2B	NM_004001.5		c.235A>T	p.Ser79Cys	missense	Exon 4 of 9	NP_003992.3
	FCGR2B	NM_001002275.3		c.232A>T	p.Ser78Cys	missense	Exon 4 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.235A>T	p.Ser79Cys	missense	Exon 3 of 8	ENSP00000351497.5	P31994-1
	FCGR2B	ENST00000367961.8	TSL:1	c.214A>T	p.Ser72Cys	missense	Exon 2 of 7	ENSP00000356938.4	P31994-3
	FCGR2B	ENST00000236937.13	TSL:1	c.235A>T	p.Ser79Cys	missense	Exon 3 of 7	ENSP00000236937.9	P31994-2

Frequencies

GnomAD3 genomes Cov.: 29

GnomAD4 exome Cov.: 31

GnomAD4 genome Cov.: 29

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
AlphaMissense	Benign	0.31
BayesDel_addAF	Benign	-0.17	T
BayesDel_noAF	Benign	-0.49
CADD	Benign	13
DANN	Uncertain	0.98
DEOGEN2	Benign	0.18	T
Eigen	Benign	-0.45
Eigen_PC	Benign	-0.69
FATHMM_MKL	Benign	0.040	N
LIST_S2	Benign	0.84	T
M_CAP	Benign	0.025	T
MetaRNN	Benign	0.17	T
MetaSVM	Benign	-1.0	T
MutationAssessor	Benign	1.8	L
PhyloP100		-1.6
PrimateAI	Benign	0.25	T
PROVEAN	Uncertain	-3.0	D
REVEL	Benign	0.052
Sift	Uncertain	0.0020	D
Sift4G	Uncertain	0.016	D
Polyphen		0.95	P
Vest4		0.30
MutPred		0.49		Loss of disorder (P = 0.0048)
MVP		0.35
MPC		1.4
ClinPred		0.62	D
GERP RS		-0.71
Varity_R		0.55
gMVP		0.19
Mutation Taster		=91/9	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: rs780661874; hg19: chr1-161641283;