rs1674761

Positions:

• chr1-161675681-A-C
• chr1-161675681-A-T

Variant summary

Our verdict is Benign. Variant got -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

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]

ACMG classification

Verdict is Benign. Variant got -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.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
FCGR2B	NM_001394477.1	c.817+368A>C		intron_variant		ENST00000358671.10	NP_001381406.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
FCGR2B	ENST00000358671.10	c.817+368A>C		intron_variant		1	NM_001394477.1	ENSP00000351497	P4
FCGR2B	ENST00000236937.13	c.760+1608A>C		intron_variant		1		ENSP00000236937	A2
FCGR2B	ENST00000367961.8	c.796+368A>C		intron_variant		1		ENSP00000356938	A2
FCGR2B	ENST00000480308.5	n.2418A>C		non_coding_transcript_exon_variant	5/6	1

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

Gnomad4 AFR exome AF: 0.760

Gnomad4 AMR exome AF: 0.855

Gnomad4 ASJ exome AF: 0.784

Gnomad4 EAS exome AF: 0.697

Gnomad4 SAS exome AF: 0.775

Gnomad4 FIN exome AF: 0.848

Gnomad4 NFE exome AF: 0.854

Gnomad4 OTH exome AF: 0.830

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

Gnomad4 AFR AF: 0.757

Gnomad4 AMR AF: 0.860

Gnomad4 ASJ AF: 0.790

Gnomad4 EAS AF: 0.787

Gnomad4 SAS AF: 0.808

Gnomad4 FIN AF: 0.892

Gnomad4 NFE AF: 0.861

Gnomad4 OTH AF: 0.843

Alfa AF: 0.813 Hom.: 2414

Bravo AF: 0.822

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.92
CADD	Benign	0.25
DANN	Benign	0.47

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

Publications

LitVar

Other links and lift over

dbSNP: rs1674761; hg19: chr1-161645471;