chr1-161675681-A-C

Variant names:

• chr1-161675681-A-C
• rs1674761
• NM_001394477.1:c.817+368A>C

Variant summary

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

The NM_001394477.1(FCGR2B):​c.817+368A>C variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.826 in 243,030 control chromosomes in the GnomAD database, including 83,268 homozygotes. In-silico tool predicts a benign outcome for this variant. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar.

• Frequency:
  • Genomes: 𝑓 0.83 (52264 hom., cov: 29)
  • Exomes 𝑓: 0.82 (31004 hom.)
• Consequence: FCGR2B NM_001394477.1 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.559
• Publications: 2 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: Benign. The variant received -12 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.92).
• BA1: GnomAd4 highest subpopulation (NFE) allele frequency at 95% confidence interval = 0.855 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.817+368A>C		intron	N/A	NP_001381406.1	P31994-1
	FCGR2B	NM_004001.5		c.817+368A>C		intron	N/A	NP_003992.3
	FCGR2B	NM_001002275.3		c.814+368A>C		intron	N/A	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.817+368A>C		intron	N/A	ENSP00000351497.5	P31994-1
	FCGR2B	ENST00000367961.8	TSL:1	c.796+368A>C		intron	N/A	ENSP00000356938.4	P31994-3
	FCGR2B	ENST00000236937.13	TSL:1	c.760+1608A>C		intron	N/A	ENSP00000236937.9	P31994-2

Frequencies

GnomAD3 genomes AF: 0.827 AC: 125592 AN: 151816 Hom.: 52221 Cov.: 29

Gnomad AFR AF: 0.757

Gnomad AMI AF: 0.662

Gnomad AMR AF: 0.859

Gnomad ASJ AF: 0.790

Gnomad EAS AF: 0.787

Gnomad SAS AF: 0.808

Gnomad FIN AF: 0.892

Gnomad MID AF: 0.807

Gnomad NFE AF: 0.861

Gnomad OTH AF: 0.842

GnomAD4 exome AF: 0.823 AC: 74941 AN: 91096 Hom.: 31004 Cov.: 0 AF XY: 0.823 AC XY: 34979 AN XY: 42482

African (AFR) AF: 0.760 AC: 3178 AN: 4182

American (AMR) AF: 0.855 AC: 2299 AN: 2688

Ashkenazi Jewish (ASJ) AF: 0.784 AC: 4248 AN: 5420

East Asian (EAS) AF: 0.697 AC: 8120 AN: 11656

South Asian (SAS) AF: 0.775 AC: 869 AN: 1122

European-Finnish (FIN) AF: 0.848 AC: 833 AN: 982

Middle Eastern (MID) AF: 0.845 AC: 465 AN: 550

European-Non Finnish (NFE) AF: 0.854 AC: 48772 AN: 57080

Other (OTH) AF: 0.830 AC: 6157 AN: 7416

GnomAD4 genome AF: 0.827 AC: 125693 AN: 151934 Hom.: 52264 Cov.: 29 AF XY: 0.829 AC XY: 61563 AN XY: 74246

African (AFR) AF: 0.757 AC: 31341 AN: 41394

American (AMR) AF: 0.860 AC: 13124 AN: 15268

Ashkenazi Jewish (ASJ) AF: 0.790 AC: 2739 AN: 3466

East Asian (EAS) AF: 0.787 AC: 4067 AN: 5168

South Asian (SAS) AF: 0.808 AC: 3884 AN: 4806

European-Finnish (FIN) AF: 0.892 AC: 9429 AN: 10568

Middle Eastern (MID) AF: 0.806 AC: 237 AN: 294

European-Non Finnish (NFE) AF: 0.861 AC: 58495 AN: 67954

Other (OTH) AF: 0.843 AC: 1775 AN: 2106

Alfa AF: 0.813 Hom.: 2414

Bravo AF: 0.822

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.92
CADD	Benign	0.25
DANN	Benign	0.47
PhyloP100		-0.56
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: rs1674761; hg19: chr1-161645471;