chr1-161506415-A-G

Variant names:

• chr1-161506415-A-G
• rs9427398
• NM_001136219.3:c.188A>G

Variant summary

Our verdict is Benign. The variant received -20 ACMG points: 0P and 20B. BP4_Strong BP6_Very_Strong BA1

The NM_001136219.3(FCGR2A):​c.188A>G​(p.Gln63Arg) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.115 in 1,613,706 control chromosomes in the GnomAD database, including 11,811 homozygotes. In-silico tool predicts a benign outcome for this variant. 15/21 in silico tools predict a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★★).

• Frequency:
  • Genomes: 𝑓 0.10 (935 hom., cov: 32)
  • Exomes 𝑓: 0.12 (10876 hom.)
• Consequence: FCGR2A NM_001136219.3 missense
• Clinical Significance: Benign criteria provided, multiple submitters, no conflicts B:3
• Conservation: PhyloP100: 0.113
• Publications: 32 publications found

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

Our verdict: Benign. The variant received -20 ACMG points.

• BP4: Computational evidence support a benign effect (MetaRNN=0.004311353).
• BP6: Variant 1-161506415-A-G is Benign according to our data. Variant chr1-161506415-A-G is described in ClinVar as Benign. ClinVar VariationId is 402850.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars.
• BA1: GnomAd4 highest subpopulation (NFE) allele frequency at 95% confidence interval = 0.121 is higher than 0.05.

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_001136219.3. 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
	FCGR2A	NM_001136219.3	MANE Select	c.188A>G	p.Gln63Arg	missense	Exon 3 of 7	NP_001129691.1
	FCGR2A	NM_021642.5		c.185A>G	p.Gln62Arg	missense	Exon 3 of 7	NP_067674.2
	FCGR2A	NM_001375296.1		c.188A>G	p.Gln63Arg	missense	Exon 3 of 6	NP_001362225.1

Ensembl Transcripts

Selected	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	FCGR2A	ENST00000271450.12	TSL:1 MANE Select	c.188A>G	p.Gln63Arg	missense	Exon 3 of 7	ENSP00000271450.6
	FCGR2A	ENST00000367972.8	TSL:1	c.185A>G	p.Gln62Arg	missense	Exon 3 of 7	ENSP00000356949.4
	FCGR2A	ENST00000699277.1		c.188A>G	p.Gln63Arg	missense	Exon 3 of 6	ENSP00000514258.1

Frequencies

GnomAD3 genomes AF: 0.101 AC: 15396 AN: 152072 Hom.: 933 Cov.: 32

Gnomad AFR AF: 0.0627

Gnomad AMI AF: 0.0779

Gnomad AMR AF: 0.104

Gnomad ASJ AF: 0.263

Gnomad EAS AF: 0.000772

Gnomad SAS AF: 0.0859

Gnomad FIN AF: 0.111

Gnomad MID AF: 0.152

Gnomad NFE AF: 0.123

Gnomad OTH AF: 0.115

GnomAD2 exomes AF: 0.108 AC: 27138 AN: 251424 AF XY: 0.112

Gnomad AFR exome AF: 0.0626

Gnomad AMR exome AF: 0.0686

Gnomad ASJ exome AF: 0.269

Gnomad EAS exome AF: 0.000544

Gnomad FIN exome AF: 0.120

Gnomad NFE exome AF: 0.131

Gnomad OTH exome AF: 0.136

GnomAD4 exome AF: 0.116 AC: 169729 AN: 1461518 Hom.: 10876 Cov.: 32 AF XY: 0.117 AC XY: 84876 AN XY: 727068

African (AFR) AF: 0.0608 AC: 2035 AN: 33448

American (AMR) AF: 0.0717 AC: 3207 AN: 44710

Ashkenazi Jewish (ASJ) AF: 0.272 AC: 7113 AN: 26124

East Asian (EAS) AF: 0.000227 AC: 9 AN: 39630

South Asian (SAS) AF: 0.0921 AC: 7946 AN: 86256

European-Finnish (FIN) AF: 0.116 AC: 6195 AN: 53414

Middle Eastern (MID) AF: 0.201 AC: 1158 AN: 5764

European-Non Finnish (NFE) AF: 0.121 AC: 134910 AN: 1111808

Other (OTH) AF: 0.119 AC: 7156 AN: 60364

GnomAD4 genome AF: 0.101 AC: 15401 AN: 152188 Hom.: 935 Cov.: 32 AF XY: 0.101 AC XY: 7536 AN XY: 74420

African (AFR) AF: 0.0628 AC: 2610 AN: 41540

American (AMR) AF: 0.104 AC: 1591 AN: 15284

Ashkenazi Jewish (ASJ) AF: 0.263 AC: 911 AN: 3470

East Asian (EAS) AF: 0.000774 AC: 4 AN: 5170

South Asian (SAS) AF: 0.0858 AC: 413 AN: 4814

European-Finnish (FIN) AF: 0.111 AC: 1175 AN: 10614

Middle Eastern (MID) AF: 0.146 AC: 43 AN: 294

European-Non Finnish (NFE) AF: 0.123 AC: 8342 AN: 67978

Other (OTH) AF: 0.114 AC: 241 AN: 2112

Alfa AF: 0.0886 Hom.: 1446

Bravo AF: 0.102

TwinsUK AF: 0.124 AC: 460

ALSPAC AF: 0.122 AC: 471

ESP6500AA AF: 0.0663 AC: 292

ESP6500EA AF: 0.132 AC: 1133

ExAC AF: 0.108 AC: 13063

Asia WGS AF: 0.0380 AC: 133 AN: 3478

EpiCase AF: 0.143

EpiControl AF: 0.148

ClinVar

Significance: Benign

Submissions summary: Benign:3

Revision: criteria provided, multiple submitters, no conflicts

Submissions by phenotype

not specified Benign:1

Mar 28, 2016

Laboratory for Molecular Medicine, Mass General Brigham Personalized Medicine

Significance: Benign

Review Status: criteria provided, single submitter

Collection Method: clinical testing

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

not provided Benign:1

Breakthrough Genomics, Breakthrough Genomics

Significance: Benign

Review Status: criteria provided, single submitter

Collection Method: not provided

FCGR2A-related disorder Benign:1

Oct 21, 2019

PreventionGenetics, part of Exact Sciences

Significance: Benign

Review Status: no assertion criteria provided

Collection Method: clinical testing

This variant is classified as benign based on ACMG/AMP sequence variant interpretation guidelines (Richards et al. 2015 PMID: 25741868, with internal and published modifications).

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
AlphaMissense	Benign	0.079
BayesDel_addAF	Benign	-0.79	T
BayesDel_noAF	Benign	-0.80
CADD	Benign	3.8
DANN	Benign	0.67
DEOGEN2	Benign	0.15	T
Eigen	Benign	-1.3
Eigen_PC	Benign	-1.3
FATHMM_MKL	Benign	0.020	N
LIST_S2	Benign	0.24	T
MetaRNN	Benign	0.0043	T
MetaSVM	Benign	-0.95	T
MutationAssessor	Benign	2.0	M
PhyloP100		0.11
PrimateAI	Benign	0.17	T
PROVEAN	Benign	-2.3	N
REVEL	Benign	0.034
Sift	Benign	0.22	T
Sift4G	Benign	0.24	T
Polyphen		0.0	B
Vest4		0.024
MPC		0.23
ClinPred		0.0065	T
GERP RS		1.3
Varity_R		0.33
gMVP		0.41
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: rs9427398; hg19: chr1-161476205; COSMIC: COSV107220785; COSMIC: COSV107220785;