rs12029217

Variant names:

• chr1-161518073-C-T
• rs12029217
• NM_001136219.3:c.879C>T

Variant summary

Our verdict is Benign. The variant received -21 ACMG points: 0P and 21B. BP4_Strong BP6_Very_Strong BP7 BA1

The NM_001136219.3(FCGR2A):​c.879C>T​(p.Pro293Pro) variant causes a synonymous change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.106 in 1,609,480 control chromosomes in the GnomAD database, including 6,199 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★★).

• Frequency:
  • Genomes: 𝑓 0.089 (416 hom., cov: 32)
  • Exomes 𝑓: 0.11 (5783 hom.)
• Consequence: FCGR2A NM_001136219.3 synonymous
• Clinical Significance: Benign criteria provided, multiple submitters, no conflicts B:2
• Conservation: PhyloP100: -0.389
• Publications: 10 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]

ENSG00000273112 (HGNC:):

ACMG classification

Our verdict: Benign. The variant received -21 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.89).
• BP6: Variant 1-161518073-C-T is Benign according to our data. Variant chr1-161518073-C-T is described in ClinVar as Benign. ClinVar VariationId is 402855.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars.
• BP7: Synonymous conserved (PhyloP=-0.389 with no splicing effect.
• BA1: GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.223 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.879C>T	p.Pro293Pro	synonymous	Exon 7 of 7	NP_001129691.1
	FCGR2A	NM_021642.5		c.876C>T	p.Pro292Pro	synonymous	Exon 7 of 7	NP_067674.2
	FCGR2A	NM_001375296.1		c.756C>T	p.Pro252Pro	synonymous	Exon 6 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.879C>T	p.Pro293Pro	synonymous	Exon 7 of 7	ENSP00000271450.6
	FCGR2A	ENST00000367972.8	TSL:1	c.876C>T	p.Pro292Pro	synonymous	Exon 7 of 7	ENSP00000356949.4
	FCGR2A	ENST00000699277.1		c.756C>T	p.Pro252Pro	synonymous	Exon 6 of 6	ENSP00000514258.1

Frequencies

GnomAD3 genomes AF: 0.0892 AC: 13515 AN: 151482 Hom.: 417 Cov.: 32

Gnomad AFR AF: 0.0326

Gnomad AMI AF: 0.209

Gnomad AMR AF: 0.0993

Gnomad ASJ AF: 0.134

Gnomad EAS AF: 0.234

Gnomad SAS AF: 0.0947

Gnomad FIN AF: 0.0637

Gnomad MID AF: 0.103

Gnomad NFE AF: 0.110

Gnomad OTH AF: 0.100

GnomAD2 exomes AF: 0.115 AC: 28660 AN: 250282 AF XY: 0.114

Gnomad AFR exome AF: 0.0319

Gnomad AMR exome AF: 0.117

Gnomad ASJ exome AF: 0.143

Gnomad EAS exome AF: 0.251

Gnomad FIN exome AF: 0.0675

Gnomad NFE exome AF: 0.116

Gnomad OTH exome AF: 0.114

GnomAD4 exome AF: 0.108 AC: 157658 AN: 1457880 Hom.: 5783 Cov.: 32 AF XY: 0.108 AC XY: 78506 AN XY: 725326

African (AFR) AF: 0.0330 AC: 1104 AN: 33452

American (AMR) AF: 0.113 AC: 5044 AN: 44596

Ashkenazi Jewish (ASJ) AF: 0.140 AC: 3646 AN: 26032

East Asian (EAS) AF: 0.227 AC: 8945 AN: 39394

South Asian (SAS) AF: 0.0899 AC: 7739 AN: 86094

European-Finnish (FIN) AF: 0.0666 AC: 3556 AN: 53360

Middle Eastern (MID) AF: 0.106 AC: 608 AN: 5754

European-Non Finnish (NFE) AF: 0.108 AC: 120197 AN: 1108952

Other (OTH) AF: 0.113 AC: 6819 AN: 60246

GnomAD4 genome AF: 0.0891 AC: 13508 AN: 151600 Hom.: 416 Cov.: 32 AF XY: 0.0886 AC XY: 6570 AN XY: 74136

African (AFR) AF: 0.0326 AC: 1351 AN: 41468

American (AMR) AF: 0.0991 AC: 1510 AN: 15236

Ashkenazi Jewish (ASJ) AF: 0.134 AC: 464 AN: 3456

East Asian (EAS) AF: 0.234 AC: 1189 AN: 5090

South Asian (SAS) AF: 0.0946 AC: 454 AN: 4800

European-Finnish (FIN) AF: 0.0637 AC: 673 AN: 10572

Middle Eastern (MID) AF: 0.103 AC: 30 AN: 290

European-Non Finnish (NFE) AF: 0.110 AC: 7439 AN: 67680

Other (OTH) AF: 0.0994 AC: 209 AN: 2102

Alfa AF: 0.112 Hom.: 225

Asia WGS AF: 0.158 AC: 548 AN: 3476

EpiCase AF: 0.126

EpiControl AF: 0.124

ClinVar

Significance: Benign

Submissions summary: Benign:2

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

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.89
CADD	Benign	1.8
DANN	Benign	0.42
PhyloP100		-0.39
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: rs12029217; hg19: chr1-161487863; COSMIC: COSV54840030;