rs4656308

Variant names:

• chr1-161508961-C-T
• rs4656308
• NM_001136219.3:c.365-859C>T

Variant summary

Our verdict is Benign. The variant received -12 ACMG points: 0P and 12B. BP4_Strong BA1

The NM_001136219.3(FCGR2A):​c.365-859C>T variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.828 in 152,192 control chromosomes in the GnomAD database, including 52,867 homozygotes. In-silico tool predicts a benign outcome for this variant. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar.

• Frequency: Genomes: 𝑓 0.83 (52867 hom., cov: 33)
• Consequence: FCGR2A NM_001136219.3 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.320
• Publications: 12 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 -12 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.99).
• BA1: GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.951 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

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	FCGR2A	NM_001136219.3	MANE Select	c.365-859C>T		intron	N/A	NP_001129691.1	P12318-1
	FCGR2A	NM_021642.5		c.362-859C>T		intron	N/A	NP_067674.2	P12318-2
	FCGR2A	NM_001375296.1		c.365-859C>T		intron	N/A	NP_001362225.1	A0A8V8TPS4

Ensembl Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	FCGR2A	ENST00000271450.12	TSL:1 MANE Select	c.365-859C>T		intron	N/A	ENSP00000271450.6	P12318-1
	FCGR2A	ENST00000367972.8	TSL:1	c.362-859C>T		intron	N/A	ENSP00000356949.4	P12318-2
	FCGR2A	ENST00000967690.1		c.365-859C>T		intron	N/A	ENSP00000637749.1

Frequencies

GnomAD3 genomes AF: 0.828 AC: 125961 AN: 152074 Hom.: 52816 Cov.: 33

Gnomad AFR AF: 0.958

Gnomad AMI AF: 0.795

Gnomad AMR AF: 0.778

Gnomad ASJ AF: 0.836

Gnomad EAS AF: 0.839

Gnomad SAS AF: 0.745

Gnomad FIN AF: 0.757

Gnomad MID AF: 0.842

Gnomad NFE AF: 0.777

Gnomad OTH AF: 0.822

We have no GnomAD4 exomes data on this position. Probably position not covered by the project.

GnomAD4 genome AF: 0.828 AC: 126068 AN: 152192 Hom.: 52867 Cov.: 33 AF XY: 0.826 AC XY: 61401 AN XY: 74380

African (AFR) AF: 0.958 AC: 39826 AN: 41554

American (AMR) AF: 0.778 AC: 11894 AN: 15296

Ashkenazi Jewish (ASJ) AF: 0.836 AC: 2902 AN: 3472

East Asian (EAS) AF: 0.840 AC: 4350 AN: 5180

South Asian (SAS) AF: 0.743 AC: 3579 AN: 4816

European-Finnish (FIN) AF: 0.757 AC: 7988 AN: 10558

Middle Eastern (MID) AF: 0.837 AC: 246 AN: 294

European-Non Finnish (NFE) AF: 0.777 AC: 52824 AN: 67996

Other (OTH) AF: 0.820 AC: 1734 AN: 2114

Alfa AF: 0.781 Hom.: 13294

Bravo AF: 0.841

Asia WGS AF: 0.779 AC: 2711 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.99
CADD	Benign	0.90
DANN	Benign	0.23
PhyloP100		-0.32
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: rs4656308; hg19: chr1-161478751;