rs10494360

Positions:

• chr1-161505960-G-A

Variant summary

Our verdict is Benign. Variant got -12 ACMG points: 0P and 12B. BP4_Strong BA1

The NM_001136219.3(FCGR2A):​c.86-27G>A variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.112 in 1,611,998 control chromosomes in the GnomAD database, including 11,451 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 0.090 (866 hom., cov: 32)
  • Exomes 𝑓: 0.11 (10585 hom.)
• Consequence: FCGR2A NM_001136219.3 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.697

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 -12 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.88).
• BA1: GnomAd4 highest subpopulation (NFE) allele frequency at 95% confidence interval = 0.12 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
FCGR2A	NM_001136219.3	c.86-27G>A		intron_variant		ENST00000271450.12

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
FCGR2A	ENST00000271450.12	c.86-27G>A		intron_variant		1	NM_001136219.3	A2

Frequencies

GnomAD3 genomes AF: 0.0901 AC: 13702 AN: 152130 Hom.: 863 Cov.: 32

Gnomad AFR AF: 0.0263

Gnomad AMI AF: 0.0780

Gnomad AMR AF: 0.0996

Gnomad ASJ AF: 0.252

Gnomad EAS AF: 0.000770

Gnomad SAS AF: 0.0851

Gnomad FIN AF: 0.111

Gnomad MID AF: 0.141

Gnomad NFE AF: 0.122

Gnomad OTH AF: 0.100

GnomAD3 exomes AF: 0.104 AC: 26141 AN: 251458 Hom.: 1810 AF XY: 0.109 AC XY: 14753 AN XY: 135900

Gnomad AFR exome AF: 0.0249

Gnomad AMR exome AF: 0.0641

Gnomad ASJ exome AF: 0.256

Gnomad EAS exome AF: 0.000218

Gnomad SAS exome AF: 0.0890

Gnomad FIN exome AF: 0.120

Gnomad NFE exome AF: 0.130

Gnomad OTH exome AF: 0.132

GnomAD4 exome AF: 0.114 AC: 166038 AN: 1459748 Hom.: 10585 Cov.: 31 AF XY: 0.115 AC XY: 83202 AN XY: 726274

Gnomad4 AFR exome AF: 0.0248

Gnomad4 AMR exome AF: 0.0672

Gnomad4 ASJ exome AF: 0.259

Gnomad4 EAS exome AF: 0.000126

Gnomad4 SAS exome AF: 0.0917

Gnomad4 FIN exome AF: 0.116

Gnomad4 NFE exome AF: 0.120

Gnomad4 OTH exome AF: 0.113

GnomAD4 genome AF: 0.0900 AC: 13706 AN: 152250 Hom.: 866 Cov.: 32 AF XY: 0.0906 AC XY: 6748 AN XY: 74444

Gnomad4 AFR AF: 0.0264

Gnomad4 AMR AF: 0.0995

Gnomad4 ASJ AF: 0.252

Gnomad4 EAS AF: 0.000772

Gnomad4 SAS AF: 0.0851

Gnomad4 FIN AF: 0.111

Gnomad4 NFE AF: 0.122

Gnomad4 OTH AF: 0.0994

Alfa AF: 0.126 Hom.: 741

Bravo AF: 0.0891

Asia WGS AF: 0.0330 AC: 116 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.88
CADD	Benign	1.3
DANN	Benign	0.53

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: rs10494360; hg19: chr1-161475750;