1-161671477-G-A

Variant names:

• chr1-161671477-G-A
• rs144573139
• NM_001394477.1:c.219G>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.219G>A​(p.Gly73Gly) variant causes a synonymous change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00686 in 1,613,888 control chromosomes in the GnomAD database, including 2 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 0.0054 (0 hom., cov: 29)
  • Exomes 𝑓: 0.0070 (2 hom.)
• Consequence: FCGR2B NM_001394477.1 synonymous
• Clinical Significance: Conflicting classifications of pathogenicity criteria provided, conflicting classifications U:1 B:1
• Conservation: PhyloP100: -0.545
• Publications: 4 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=-0.84).
• BP6: Variant 1-161671477-G-A is Benign according to our data. Variant chr1-161671477-G-A is described in ClinVar as Conflicting_classifications_of_pathogenicity. ClinVar VariationId is 806265.
• BP7: Synonymous conserved (PhyloP=-0.545 with no splicing effect.
• BS2: High Homozygotes in GnomAdExome4 at 2 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.219G>A	p.Gly73Gly	synonymous	Exon 3 of 8	NP_001381406.1	P31994-1
	FCGR2B	NM_004001.5		c.219G>A	p.Gly73Gly	synonymous	Exon 4 of 9	NP_003992.3
	FCGR2B	NM_001002275.3		c.216G>A	p.Gly72Gly	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.219G>A	p.Gly73Gly	synonymous	Exon 3 of 8	ENSP00000351497.5	P31994-1
	FCGR2B	ENST00000367961.8	TSL:1	c.198G>A	p.Gly66Gly	synonymous	Exon 2 of 7	ENSP00000356938.4	P31994-3
	FCGR2B	ENST00000236937.13	TSL:1	c.219G>A	p.Gly73Gly	synonymous	Exon 3 of 7	ENSP00000236937.9	P31994-2

Frequencies

GnomAD3 genomes AF: 0.00540 AC: 822 AN: 152130 Hom.: 0 Cov.: 29

Gnomad AFR AF: 0.00128

Gnomad AMI AF: 0.00329

Gnomad AMR AF: 0.00897

Gnomad ASJ AF: 0.00893

Gnomad EAS AF: 0.00

Gnomad SAS AF: 0.00517

Gnomad FIN AF: 0.000377

Gnomad MID AF: 0.00949

Gnomad NFE AF: 0.00798

Gnomad OTH AF: 0.0110

GnomAD2 exomes AF: 0.00528 AC: 1327 AN: 251438 AF XY: 0.00540

Gnomad AFR exome AF: 0.000923

Gnomad AMR exome AF: 0.00448

Gnomad ASJ exome AF: 0.0136

Gnomad EAS exome AF: 0.000218

Gnomad FIN exome AF: 0.000370

Gnomad NFE exome AF: 0.00731

Gnomad OTH exome AF: 0.00733

GnomAD4 exome AF: 0.00702 AC: 10258 AN: 1461640 Hom.: 2 Cov.: 31 AF XY: 0.00695 AC XY: 5052 AN XY: 727124

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

African (AFR) AF: 0.00149 AC: 50 AN: 33480

American (AMR) AF: 0.00445 AC: 199 AN: 44720

Ashkenazi Jewish (ASJ) AF: 0.0113 AC: 295 AN: 26134

East Asian (EAS) AF: 0.000101 AC: 4 AN: 39694

South Asian (SAS) AF: 0.00452 AC: 390 AN: 86250

European-Finnish (FIN) AF: 0.000543 AC: 29 AN: 53420

Middle Eastern (MID) AF: 0.0160 AC: 92 AN: 5766

European-Non Finnish (NFE) AF: 0.00783 AC: 8708 AN: 1111788

Other (OTH) AF: 0.00813 AC: 491 AN: 60388

⚠️ 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: 0.00539 AC: 821 AN: 152248 Hom.: 0 Cov.: 29 AF XY: 0.00517 AC XY: 385 AN XY: 74440

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

African (AFR) AF: 0.00128 AC: 53 AN: 41546

American (AMR) AF: 0.00896 AC: 137 AN: 15286

Ashkenazi Jewish (ASJ) AF: 0.00893 AC: 31 AN: 3470

East Asian (EAS) AF: 0.00 AC: 0 AN: 5174

South Asian (SAS) AF: 0.00497 AC: 24 AN: 4828

European-Finnish (FIN) AF: 0.000377 AC: 4 AN: 10612

Middle Eastern (MID) AF: 0.0102 AC: 3 AN: 294

European-Non Finnish (NFE) AF: 0.00798 AC: 543 AN: 68012

Other (OTH) AF: 0.0109 AC: 23 AN: 2114

⚠️ 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: 0.00783 Hom.: 1

EpiCase AF: 0.00992

EpiControl AF: 0.00890

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	-0.84
CADD	Benign	1.0
DANN	Benign	0.78
PhyloP100		-0.55
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: rs144573139; hg19: chr1-161641267; COSMIC: COSV52683461; COSMIC: COSV52683461;