1-161510859-A-G

Variant summary

Our verdict is Benign. Variant got -15 ACMG points: 0P and 15B. BP4_Strong BP6_Moderate BP7 BA1

The NM_001136219.3(FCGR2A):c.645A>G(p.Pro215=) variant causes a synonymous change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.111 in 1,614,006 control chromosomes in the GnomAD database, including 11,351 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★).

• Frequency:
  • Genomes: 𝑓 0.088 (869 hom., cov: 33)
  • Exomes 𝑓: 0.11 (10482 hom.)
• Consequence: FCGR2A NM_001136219.3 synonymous
• Clinical Significance: Benign criteria provided, single submitter B:1
• Conservation: PhyloP100: -0.233

Genes affected

FCGR2A (HGNC:3616): (Fc gamma receptor IIa) This gene encodes one member of a family of immunoglobulin Fc receptor genes found on the surface of many immune response cells. The protein encoded by this gene is a cell surface receptor found on phagocytic cells such as macrophages and neutrophils, and is involved in the process of phagocytosis and clearing of immune complexes. Alternative splicing results in multiple transcript variants. [provided by RefSeq, Oct 2008]

ACMG classification

Verdict is Benign. Variant got -15 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.94).
• BP6: Variant 1-161510859-A-G is Benign according to our data. Variant chr1-161510859-A-G is described in ClinVar as [Benign]. Clinvar id is 402854.Status of the report is criteria_provided_single_submitter, 1 stars.
• BP7: Synonymous conserved (PhyloP=-0.233 with no splicing effect.
• BA1: GnomAd4 highest subpopulation (NFE) allele frequency at 95% confidence interval = 0.12 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
FCGR2A	NM_001136219.3	c.645A>G	p.Pro215=	synonymous_variant	5/7	ENST00000271450.12

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
FCGR2A	ENST00000271450.12	c.645A>G	p.Pro215=	synonymous_variant	5/7	1	NM_001136219.3	A2

Frequencies

GnomAD3 genomes AF: 0.0883 AC: 13434 AN: 152092 Hom.: 869 Cov.: 33

Gnomad AFR AF: 0.0213

Gnomad AMI AF: 0.0779

Gnomad AMR AF: 0.0988

Gnomad ASJ AF: 0.244

Gnomad EAS AF: 0.000770

Gnomad SAS AF: 0.0853

Gnomad FIN AF: 0.109

Gnomad MID AF: 0.149

Gnomad NFE AF: 0.122

Gnomad OTH AF: 0.100

GnomAD3 exomes AF: 0.103 AC: 25952 AN: 251426 Hom.: 1790 AF XY: 0.108 AC XY: 14680 AN XY: 135882

Gnomad AFR exome AF: 0.0191

Gnomad AMR exome AF: 0.0643

Gnomad ASJ exome AF: 0.248

Gnomad EAS exome AF: 0.000381

Gnomad SAS exome AF: 0.0892

Gnomad FIN exome AF: 0.119

Gnomad NFE exome AF: 0.130

Gnomad OTH exome AF: 0.131

GnomAD4 exome AF: 0.114 AC: 166188 AN: 1461796 Hom.: 10482 Cov.: 32 AF XY: 0.114 AC XY: 83244 AN XY: 727202

Gnomad4 AFR exome AF: 0.0183

Gnomad4 AMR exome AF: 0.0672

Gnomad4 ASJ exome AF: 0.251

Gnomad4 EAS exome AF: 0.000176

Gnomad4 SAS exome AF: 0.0920

Gnomad4 FIN exome AF: 0.115

Gnomad4 NFE exome AF: 0.121

Gnomad4 OTH exome AF: 0.111

GnomAD4 genome AF: 0.0882 AC: 13428 AN: 152210 Hom.: 869 Cov.: 33 AF XY: 0.0890 AC XY: 6621 AN XY: 74420

Gnomad4 AFR AF: 0.0212

Gnomad4 AMR AF: 0.0986

Gnomad4 ASJ AF: 0.244

Gnomad4 EAS AF: 0.000772

Gnomad4 SAS AF: 0.0854

Gnomad4 FIN AF: 0.109

Gnomad4 NFE AF: 0.122

Gnomad4 OTH AF: 0.0999

Alfa AF: 0.129 Hom.: 592

Bravo AF: 0.0867

Asia WGS AF: 0.0290 AC: 105 AN: 3478

EpiCase AF: 0.142

EpiControl AF: 0.147

ClinVar

Significance: Benign

Submissions summary: Benign:1

Revision: criteria provided, single submitter

Submissions by phenotype

not specified Benign:1

Benign, criteria provided, single submitter

clinical testing

Laboratory for Molecular Medicine, Mass General Brigham Personalized Medicine

Mar 28, 2016

Variant identified in a genome or exome case(s) and assessed due to predicted null impact of the variant or pathogenic assertions in the literature or databases. Disclaimer: This variant has not undergone full assessment. The following are preliminary notes: Frequency -

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.94
Cadd	Benign	1.2
Dann	Benign	0.39
RBP_binding_hub_radar		0.0
RBP_regulation_power_radar		1.1

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: rs11810143; hg19: chr1-161480649;