1-161506371-G-C

Variant names:

• chr1-161506371-G-C
• rs553243113
• NM_001136219.3:c.144G>C

Variant summary

Our verdict is Likely benign. The variant received -3 ACMG points: 2P and 5B. PM2 BP4_Strong BP7

The NM_001136219.3(FCGR2A):​c.144G>C​(p.Pro48Pro) variant causes a synonymous change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.000000684 in 1,461,894 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a benign outcome for this variant. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar. Synonymous variant affecting the same amino acid position (i.e. P48P) has been classified as Likely benign.

• Frequency:
  • Genomes: not found (cov: 32)
  • Exomes 𝑓: 6.8e-7 (0 hom.)
• Consequence: FCGR2A NM_001136219.3 synonymous
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -2.25
• Publications: 0 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: Likely_benign. The variant received -3 ACMG points.

• PM2: Very rare variant in population databases, with high coverage
• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.66).
• BP7: Synonymous conserved (PhyloP=-2.25 with no splicing effect.

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.144G>C	p.Pro48Pro	synonymous	Exon 3 of 7	NP_001129691.1	P12318-1
	FCGR2A	NM_021642.5		c.141G>C	p.Pro47Pro	synonymous	Exon 3 of 7	NP_067674.2	P12318-2
	FCGR2A	NM_001375296.1		c.144G>C	p.Pro48Pro	synonymous	Exon 3 of 6	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.144G>C	p.Pro48Pro	synonymous	Exon 3 of 7	ENSP00000271450.6	P12318-1
	FCGR2A	ENST00000367972.8	TSL:1	c.141G>C	p.Pro47Pro	synonymous	Exon 3 of 7	ENSP00000356949.4	P12318-2
	FCGR2A	ENST00000699279.1		c.-274G>C		5_prime_UTR_premature_start_codon_gain	Exon 2 of 6	ENSP00000514260.1	A0A8V8TN30

Frequencies

GnomAD3 genomes Cov.: 32

GnomAD4 exome AF: 6.84e-7 AC: 1 AN: 1461894 Hom.: 0 Cov.: 31 AF XY: 0.00000138 AC XY: 1 AN XY: 727248

African (AFR) AF: 0.00 AC: 0 AN: 33480

American (AMR) AF: 0.00 AC: 0 AN: 44724

Ashkenazi Jewish (ASJ) AF: 0.00 AC: 0 AN: 26136

East Asian (EAS) AF: 0.00 AC: 0 AN: 39700

South Asian (SAS) AF: 0.00 AC: 0 AN: 86258

European-Finnish (FIN) AF: 0.00 AC: 0 AN: 53420

Middle Eastern (MID) AF: 0.00 AC: 0 AN: 5768

European-Non Finnish (NFE) AF: 8.99e-7 AC: 1 AN: 1112012

Other (OTH) AF: 0.00 AC: 0 AN: 60396

GnomAD4 genome Cov.: 32

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.66
CADD	Benign	1.9
DANN	Benign	0.77
PhyloP100		-2.2
RBP_binding_hub_radar		0.0
RBP_regulation_power_radar		1.7
Mutation Taster		=100/0	polymorphism

Splicing

Name	Calibrated prediction	Score	Prediction
SpliceAI score (max)		0.010		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: rs553243113; hg19: chr1-161476161;