1-161677743-A-G

Variant names:

• chr1-161677743-A-G
• rs844
• ENST00000480308.5:n.4370A>G

Variant summary

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

The ENST00000480308.5(FCGR2B):​n.4370A>G variant causes a non coding transcript exon change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.701 in 560,504 control chromosomes in the GnomAD database, including 138,188 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 0.71 (38323 hom., cov: 31)
  • Exomes 𝑓: 0.70 (99865 hom.)
• Consequence: FCGR2B ENST00000480308.5 non_coding_transcript_exon
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 0.0790
• Publications: 20 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: Labcorp Genetics (formerly Invitae), Orphanet

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 (AMR) allele frequency at 95% confidence interval = 0.754 is higher than 0.05.

Variant Effect in Transcripts

ACMG analysis was done for transcript: ENST00000480308.5. You can select a different transcript below to see updated ACMG assignments.

RefSeq Transcripts

Selected	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	FCGR2B	NM_001394477.1	MANE Select	c.*190A>G		3_prime_UTR	Exon 8 of 8	NP_001381406.1
	FCGR2B	NR_169827.1		n.1352A>G		non_coding_transcript_exon	Exon 10 of 10
	FCGR2B	NM_004001.5		c.*190A>G		3_prime_UTR	Exon 9 of 9	NP_003992.3

Ensembl Transcripts

Selected	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	FCGR2B	ENST00000480308.5	TSL:1	n.4370A>G		non_coding_transcript_exon	Exon 6 of 6
	FCGR2B	ENST00000358671.10	TSL:1 MANE Select	c.*190A>G		3_prime_UTR	Exon 8 of 8	ENSP00000351497.5
	FCGR2B	ENST00000367961.8	TSL:1	c.*190A>G		3_prime_UTR	Exon 7 of 7	ENSP00000356938.4

Frequencies

GnomAD3 genomes AF: 0.709 AC: 107698 AN: 151928 Hom.: 38278 Cov.: 31

Gnomad AFR AF: 0.713

Gnomad AMI AF: 0.601

Gnomad AMR AF: 0.765

Gnomad ASJ AF: 0.686

Gnomad EAS AF: 0.738

Gnomad SAS AF: 0.702

Gnomad FIN AF: 0.729

Gnomad MID AF: 0.713

Gnomad NFE AF: 0.691

Gnomad OTH AF: 0.714

GnomAD4 exome AF: 0.698 AC: 284916 AN: 408458 Hom.: 99865 Cov.: 4 AF XY: 0.699 AC XY: 149206 AN XY: 213394

African (AFR) AF: 0.712 AC: 7730 AN: 10860

American (AMR) AF: 0.767 AC: 10192 AN: 13284

Ashkenazi Jewish (ASJ) AF: 0.693 AC: 9046 AN: 13048

East Asian (EAS) AF: 0.664 AC: 18648 AN: 28098

South Asian (SAS) AF: 0.703 AC: 24366 AN: 34638

European-Finnish (FIN) AF: 0.731 AC: 22003 AN: 30090

Middle Eastern (MID) AF: 0.750 AC: 1401 AN: 1868

European-Non Finnish (NFE) AF: 0.692 AC: 174634 AN: 252434

Other (OTH) AF: 0.700 AC: 16896 AN: 24138

GnomAD4 genome AF: 0.709 AC: 107803 AN: 152046 Hom.: 38323 Cov.: 31 AF XY: 0.714 AC XY: 53039 AN XY: 74308

African (AFR) AF: 0.714 AC: 29577 AN: 41450

American (AMR) AF: 0.765 AC: 11703 AN: 15296

Ashkenazi Jewish (ASJ) AF: 0.686 AC: 2376 AN: 3466

East Asian (EAS) AF: 0.739 AC: 3810 AN: 5158

South Asian (SAS) AF: 0.702 AC: 3382 AN: 4818

European-Finnish (FIN) AF: 0.729 AC: 7709 AN: 10570

Middle Eastern (MID) AF: 0.719 AC: 210 AN: 292

European-Non Finnish (NFE) AF: 0.691 AC: 46974 AN: 67976

Other (OTH) AF: 0.718 AC: 1516 AN: 2112

Alfa AF: 0.667 Hom.: 4446

Bravo AF: 0.711

Asia WGS AF: 0.715 AC: 2490 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.92
CADD	Benign	3.5
DANN	Benign	0.61
PhyloP100		0.079
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: rs844; hg19: chr1-161647533;