1-161509955-A-G

Variant summary

Our verdict is Benign. Variant got -14 ACMG points: 0P and 14B. BP4_Strong BP6_Moderate BA1

The NM_001136219.3(FCGR2A):c.500A>G(p.His167Arg) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.503 in 1,613,712 control chromosomes in the GnomAD database, including 206,994 homozygotes. In-silico tool predicts a benign outcome for this variant. 13/20 in silico tools predict a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★).

• Frequency:
  • Genomes: 𝑓 0.50 (19465 hom., cov: 32)
  • Exomes 𝑓: 0.50 (187529 hom.)
• Consequence: FCGR2A NM_001136219.3 missense
• Clinical Significance: Benign criteria provided, single submitter B:1 O:3
• Conservation: PhyloP100: -0.458

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 -14 ACMG points.

• BP4: Computational evidence support a benign effect (MetaRNN=4.473957E-5).
• BP6: Variant 1-161509955-A-G is Benign according to our data. Variant chr1-161509955-A-G is described in ClinVar as [Benign]. Clinvar id is 14823.Status of the report is criteria_provided_single_submitter, 1 stars.
• BA1: GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.536 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
FCGR2A	NM_001136219.3	c.500A>G	p.His167Arg	missense_variant	4/7	ENST00000271450.12

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
FCGR2A	ENST00000271450.12	c.500A>G	p.His167Arg	missense_variant	4/7	1	NM_001136219.3	A2

Frequencies

GnomAD3 genomes AF: 0.502 AC: 76314 AN: 151928 Hom.: 19447 Cov.: 32

Gnomad AFR AF: 0.542

Gnomad AMI AF: 0.368

Gnomad AMR AF: 0.488

Gnomad ASJ AF: 0.422

Gnomad EAS AF: 0.304

Gnomad SAS AF: 0.401

Gnomad FIN AF: 0.512

Gnomad MID AF: 0.522

Gnomad NFE AF: 0.508

Gnomad OTH AF: 0.492

GnomAD3 exomes AF: 0.476 AC: 119499 AN: 251224 Hom.: 29024 AF XY: 0.471 AC XY: 63904 AN XY: 135776

Gnomad AFR exome AF: 0.547

Gnomad AMR exome AF: 0.517

Gnomad ASJ exome AF: 0.405

Gnomad EAS exome AF: 0.326

Gnomad SAS exome AF: 0.417

Gnomad FIN exome AF: 0.489

Gnomad NFE exome AF: 0.497

Gnomad OTH exome AF: 0.474

GnomAD4 exome AF: 0.503 AC: 734636 AN: 1461666 Hom.: 187529 Cov.: 106 AF XY: 0.498 AC XY: 361788 AN XY: 727142

Gnomad4 AFR exome AF: 0.550

Gnomad4 AMR exome AF: 0.513

Gnomad4 ASJ exome AF: 0.403

Gnomad4 EAS exome AF: 0.254

Gnomad4 SAS exome AF: 0.416

Gnomad4 FIN exome AF: 0.499

Gnomad4 NFE exome AF: 0.519

Gnomad4 OTH exome AF: 0.503

GnomAD4 genome AF: 0.502 AC: 76380 AN: 152046 Hom.: 19465 Cov.: 32 AF XY: 0.498 AC XY: 37037 AN XY: 74304

Gnomad4 AFR AF: 0.542

Gnomad4 AMR AF: 0.488

Gnomad4 ASJ AF: 0.422

Gnomad4 EAS AF: 0.305

Gnomad4 SAS AF: 0.400

Gnomad4 FIN AF: 0.512

Gnomad4 NFE AF: 0.508

Gnomad4 OTH AF: 0.492

Alfa AF: 0.490 Hom.: 43540

Bravo AF: 0.508

TwinsUK AF: 0.530 AC: 1964

ALSPAC AF: 0.533 AC: 2054

ESP6500AA AF: 0.558 AC: 2460

ESP6500EA AF: 0.517 AC: 4446

ExAC AF: 0.479 AC: 58150

Asia WGS AF: 0.383 AC: 1334 AN: 3478

EpiCase AF: 0.485

EpiControl AF: 0.480

ClinVar

Significance: Benign

Submissions summary: Benign:1 Other:3

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: Variant reported as a risk factor for lupus nephritis, severe malaria, p. aeurginosa infection, and reduced risk for ulcerative colitis - questionable and unrelated to patient disease. -

Lupus nephritis, susceptibility to Other:1

risk factor, no assertion criteria provided

literature only

OMIM

Jul 01, 2010

- -

Pseudomonas aeruginosa, susceptibility to chronic infection by, in cystic fibrosis Other:1

risk factor, no assertion criteria provided

literature only

OMIM

Jul 01, 2010

- -

Malaria, severe, susceptibility to Other:1

risk factor, no assertion criteria provided

literature only

OMIM

Jul 01, 2010

- -

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
AlphaMissense	Benign	0.10
BayesDel_addAF	Benign	-0.81	T
BayesDel_noAF	Benign	-0.79
Cadd	Benign	0.0020
Dann	Benign	0.23
Eigen	Benign	-1.4
Eigen_PC	Benign	-1.5
FATHMM_MKL	Benign	0.0090	N
LIST_S2	Benign	0.021	T;T
MetaRNN	Benign	0.000045	T;T
MetaSVM	Benign	-0.96	T
MutationTaster	Benign	1.0	P;P
PrimateAI	Benign	0.30	T
PROVEAN	Uncertain	-3.1	D;D
REVEL	Benign	0.053
Sift	Benign	0.17	T;T
Sift4G	Benign	0.47	T;T
Polyphen		0.0	B;B
Vest4		0.031
MPC		0.26
ClinPred		0.026	T
GERP RS		-4.2
RBP_binding_hub_radar		0.0
RBP_regulation_power_radar		1.1
Varity_R		0.47
gMVP		0.58

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: rs1801274; hg19: chr1-161479745; COSMIC: COSV54837119; COSMIC: COSV54837119;