rs10494360

Variant names:

• chr1-161505960-G-A
• rs10494360
• NM_001136219.3:c.86-27G>A

Variant summary

Our verdict is Benign. The variant received -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
• Publications: 33 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=-0.88).
• BA1: GnomAd4 highest subpopulation (NFE) allele frequency at 95% confidence interval = 0.12 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.86-27G>A		intron	N/A	NP_001129691.1
	FCGR2A	NM_021642.5		c.86-27G>A		intron	N/A	NP_067674.2
	FCGR2A	NM_001375296.1		c.86-27G>A		intron	N/A	NP_001362225.1

Ensembl Transcripts

Selected	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	FCGR2A	ENST00000271450.12	TSL:1 MANE Select	c.86-27G>A		intron	N/A	ENSP00000271450.6
	FCGR2A	ENST00000367972.8	TSL:1	c.86-27G>A		intron	N/A	ENSP00000356949.4
	FCGR2A	ENST00000473080.1	TSL:2	n.508G>A		non_coding_transcript_exon	Exon 1 of 2

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

GnomAD2 exomes AF: 0.104 AC: 26141 AN: 251458 AF XY: 0.109

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 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

African (AFR) AF: 0.0248 AC: 829 AN: 33464

American (AMR) AF: 0.0672 AC: 3005 AN: 44722

Ashkenazi Jewish (ASJ) AF: 0.259 AC: 6748 AN: 26094

East Asian (EAS) AF: 0.000126 AC: 5 AN: 39690

South Asian (SAS) AF: 0.0917 AC: 7909 AN: 86234

European-Finnish (FIN) AF: 0.116 AC: 6196 AN: 53410

Middle Eastern (MID) AF: 0.190 AC: 1097 AN: 5762

European-Non Finnish (NFE) AF: 0.120 AC: 133439 AN: 1110024

Other (OTH) AF: 0.113 AC: 6810 AN: 60348

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

African (AFR) AF: 0.0264 AC: 1095 AN: 41538

American (AMR) AF: 0.0995 AC: 1522 AN: 15298

Ashkenazi Jewish (ASJ) AF: 0.252 AC: 873 AN: 3466

East Asian (EAS) AF: 0.000772 AC: 4 AN: 5184

South Asian (SAS) AF: 0.0851 AC: 411 AN: 4828

European-Finnish (FIN) AF: 0.111 AC: 1173 AN: 10614

Middle Eastern (MID) AF: 0.140 AC: 41 AN: 292

European-Non Finnish (NFE) AF: 0.122 AC: 8306 AN: 68008

Other (OTH) AF: 0.0994 AC: 210 AN: 2112

Alfa AF: 0.125 Hom.: 807

Bravo AF: 0.0891

Asia WGS AF: 0.0330 AC: 116 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.88
CADD	Benign	1.3
DANN	Benign	0.53
PhyloP100		-0.70
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: rs10494360; hg19: chr1-161475750;