NM_001394477.1:c.189G>A

Variant names:

• chr1-161671447-G-A
• rs5017568
• NM_001394477.1:c.189G>A

Variant summary

Our verdict is Benign. The variant received -10 ACMG points: 0P and 10B. BP4_Strong BP6 BP7 BS2

The NM_001394477.1(FCGR2B):​c.189G>A​(p.Gln63Gln) variant causes a synonymous change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00618 in 1,603,124 control chromosomes in the GnomAD database, including 4 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Conflicting classifications of pathogenicity (no stars).

• Frequency:
  • Genomes: 𝑓 0.0064 (0 hom., cov: 29)
  • Exomes 𝑓: 0.0062 (4 hom.)
• Consequence: FCGR2B NM_001394477.1 synonymous
• Clinical Significance: Conflicting classifications of pathogenicity criteria provided, conflicting classifications U:1 B:1
• Conservation: PhyloP100: 0.746
• Publications: 3 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 -10 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.85).
• BP6: Variant 1-161671447-G-A is Benign according to our data. Variant chr1-161671447-G-A is described in ClinVar as Conflicting_classifications_of_pathogenicity. ClinVar VariationId is 806264.
• BP7: Synonymous conserved (PhyloP=0.746 with no splicing effect.
• BS2: High Homozygotes in GnomAdExome4 at 4 Unknown gene

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.189G>A	p.Gln63Gln	synonymous	Exon 3 of 8	NP_001381406.1	P31994-1
	FCGR2B	NM_004001.5		c.189G>A	p.Gln63Gln	synonymous	Exon 4 of 9	NP_003992.3
	FCGR2B	NM_001002275.3		c.186G>A	p.Gln62Gln	synonymous	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.189G>A	p.Gln63Gln	synonymous	Exon 3 of 8	ENSP00000351497.5	P31994-1
	FCGR2B	ENST00000367961.8	TSL:1	c.168G>A	p.Gln56Gln	synonymous	Exon 2 of 7	ENSP00000356938.4	P31994-3
	FCGR2B	ENST00000236937.13	TSL:1	c.189G>A	p.Gln63Gln	synonymous	Exon 3 of 7	ENSP00000236937.9	P31994-2

Frequencies

GnomAD3 genomes AF: 0.00641 AC: 973 AN: 151796 Hom.: 0 Cov.: 29

Gnomad AFR AF: 0.00212

Gnomad AMI AF: 0.00439

Gnomad AMR AF: 0.00841

Gnomad ASJ AF: 0.0145

Gnomad EAS AF: 0.000192

Gnomad SAS AF: 0.00768

Gnomad FIN AF: 0.000377

Gnomad MID AF: 0.0129

Gnomad NFE AF: 0.00940

Gnomad OTH AF: 0.00962

GnomAD2 exomes AF: 0.00278 AC: 693 AN: 249478 AF XY: 0.00277

Gnomad AFR exome AF: 0.00136

Gnomad AMR exome AF: 0.00281

Gnomad ASJ exome AF: 0.00478

Gnomad EAS exome AF: 0.0000544

Gnomad FIN exome AF: 0.000416

Gnomad NFE exome AF: 0.00374

Gnomad OTH exome AF: 0.00477

GnomAD4 exome AF: 0.00615 AC: 8928 AN: 1451206 Hom.: 4 Cov.: 31 AF XY: 0.00618 AC XY: 4459 AN XY: 721994

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

African (AFR) AF: 0.00179 AC: 60 AN: 33456

American (AMR) AF: 0.00366 AC: 163 AN: 44562

Ashkenazi Jewish (ASJ) AF: 0.0105 AC: 269 AN: 25702

East Asian (EAS) AF: 0.000227 AC: 9 AN: 39690

South Asian (SAS) AF: 0.00533 AC: 457 AN: 85794

European-Finnish (FIN) AF: 0.000880 AC: 47 AN: 53384

Middle Eastern (MID) AF: 0.0130 AC: 74 AN: 5708

European-Non Finnish (NFE) AF: 0.00672 AC: 7412 AN: 1102994

Other (OTH) AF: 0.00729 AC: 437 AN: 59916

⚠️ 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: 0.00641 AC: 974 AN: 151918 Hom.: 0 Cov.: 29 AF XY: 0.00598 AC XY: 444 AN XY: 74280

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

African (AFR) AF: 0.00212 AC: 88 AN: 41534

American (AMR) AF: 0.00840 AC: 128 AN: 15236

Ashkenazi Jewish (ASJ) AF: 0.0145 AC: 50 AN: 3442

East Asian (EAS) AF: 0.000193 AC: 1 AN: 5184

South Asian (SAS) AF: 0.00809 AC: 39 AN: 4820

European-Finnish (FIN) AF: 0.000377 AC: 4 AN: 10622

Middle Eastern (MID) AF: 0.0139 AC: 4 AN: 288

European-Non Finnish (NFE) AF: 0.00940 AC: 637 AN: 67778

Other (OTH) AF: 0.00904 AC: 19 AN: 2102

⚠️ 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: 0.00904 Hom.: 0

ClinVar

ClinVar submissions

Significance: Conflicting classifications of pathogenicity

Revision: criteria provided, conflicting classifications

Pathogenic	VUS	Benign	Condition
-	1	1	not provided (2)

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.85
CADD	Benign	7.0
DANN	Benign	0.66
PhyloP100		0.75
Mutation Taster		=100/0	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: rs5017568; hg19: chr1-161641237; COSMIC: COSV52681235; COSMIC: COSV52681235;