rs382627

Variant names:

• chr1-161518015-T-C
• rs382627
• NM_001136219.3:c.821T>C

Your query was ambiguous. Multiple possible variants found:

• chr1-161518015-T-C
• chr1-161518015-T-G

Variant summary

Our verdict is Likely benign. The variant received -2 ACMG points: 2P and 4B. PM2 BP4_Strong

The NM_001136219.3(FCGR2A):​c.821T>C​(p.Leu274Pro) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0259 in 93,258 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a benign outcome for this variant. 16/22 in silico tools predict a benign outcome for this variant. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar.

• Frequency:
  • Genomes: 𝑓 0.026 (0 hom., cov: 30)
  • Exomes 𝑓: 0.0048 (12 hom.)
  • Failed GnomAD Quality Control
• Consequence: FCGR2A NM_001136219.3 missense
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.131
• Publications: 23 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: Likely_benign. The variant received -2 ACMG points.

• PM2: Variant has high frequency in the SAS (0.0435) population. However there is too low homozygotes in high coverage region: (expected more than 15, got 0).
• BP4: Computational evidence support a benign effect (MetaRNN=0.0043204427).

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
FCGR2A	NM_001136219.3	c.821T>C	p.Leu274Pro	missense_variant	Exon 7 of 7	ENST00000271450.12	NP_001129691.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
FCGR2A	ENST00000271450.12	c.821T>C	p.Leu274Pro	missense_variant	Exon 7 of 7	1	NM_001136219.3	ENSP00000271450.6

Frequencies

GnomAD3 genomes AF: 0.0259 AC: 2414 AN: 93134 Hom.: 0 Cov.: 30

Gnomad AFR AF: 0.0174

Gnomad AMI AF: 0.0236

Gnomad AMR AF: 0.0297

Gnomad ASJ AF: 0.0252

Gnomad EAS AF: 0.0487

Gnomad SAS AF: 0.0505

Gnomad FIN AF: 0.0167

Gnomad MID AF: 0.0417

Gnomad NFE AF: 0.0291

Gnomad OTH AF: 0.0256

GnomAD2 exomes AF: 0.000429 AC: 103 AN: 239870 AF XY: 0.000385

Gnomad AFR exome AF: 0.000386

Gnomad AMR exome AF: 0.000854

Gnomad ASJ exome AF: 0.000103

Gnomad EAS exome AF: 0.000709

Gnomad FIN exome AF: 0.00

Gnomad NFE exome AF: 0.000313

Gnomad OTH exome AF: 0.000690

GnomAD4 exome Data not reliable, filtered out with message: AS_VQSR AF: 0.00475 AC: 5929 AN: 1247730 Hom.: 12 Cov.: 31 AF XY: 0.00486 AC XY: 2994 AN XY: 615858

⚠️ The allele balance in gnomAD version 4 Exomes is significantly skewed from the expected value of 0.5.

African (AFR) AF: 0.00390 AC: 109 AN: 27916

American (AMR) AF: 0.00995 AC: 325 AN: 32654

Ashkenazi Jewish (ASJ) AF: 0.0124 AC: 221 AN: 17872

East Asian (EAS) AF: 0.0111 AC: 316 AN: 28374

South Asian (SAS) AF: 0.00589 AC: 392 AN: 66556

European-Finnish (FIN) AF: 0.00705 AC: 280 AN: 39726

Middle Eastern (MID) AF: 0.00319 AC: 15 AN: 4708

European-Non Finnish (NFE) AF: 0.00403 AC: 3955 AN: 981972

Other (OTH) AF: 0.00659 AC: 316 AN: 47952

⚠️ The allele balance in gnomAD4 Exomes is highly skewed from 0.5 (p-value = 0), which strongly suggests a high chance of mosaicism in these individuals.

GnomAD4 genome AF: 0.0259 AC: 2419 AN: 93258 Hom.: 0 Cov.: 30 AF XY: 0.0258 AC XY: 1182 AN XY: 45854

⚠️ The allele balance in gnomAD version 4 Genomes is significantly skewed from the expected value of 0.5.

African (AFR) AF: 0.0174 AC: 472 AN: 27078

American (AMR) AF: 0.0297 AC: 271 AN: 9112

Ashkenazi Jewish (ASJ) AF: 0.0252 AC: 47 AN: 1866

East Asian (EAS) AF: 0.0486 AC: 151 AN: 3106

South Asian (SAS) AF: 0.0505 AC: 133 AN: 2636

European-Finnish (FIN) AF: 0.0167 AC: 122 AN: 7326

Middle Eastern (MID) AF: 0.0368 AC: 5 AN: 136

European-Non Finnish (NFE) AF: 0.0291 AC: 1173 AN: 40336

Other (OTH) AF: 0.0284 AC: 34 AN: 1196

⚠️ The allele balance in gnomAD version 4 Genomes is significantly skewed from the expected value of 0.5. (p-value = 0), which strongly suggests a high chance of mosaicism in these individuals.

Alfa AF: 0.0646 Hom.: 0

ExAC AF: 0.000346 AC: 42

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
AlphaMissense	Benign	0.052
BayesDel_addAF	Benign	-0.49	T
BayesDel_noAF	Benign	-0.54
CADD	Benign	3.3
DANN	Benign	0.18
DEOGEN2	Benign	0.031	.;T
Eigen	Benign	-1.6
Eigen_PC	Benign	-1.7
FATHMM_MKL	Benign	0.0021	N
LIST_S2	Benign	0.45	T;T
M_CAP	Benign	0.0043	T
MetaRNN	Benign	0.0043	T;T
MetaSVM	Benign	-0.90	T
MutationAssessor	Benign	0.0	.;N
PhyloP100		-0.13
PrimateAI	Benign	0.40	T
PROVEAN	Benign	1.4	N;N
REVEL	Benign	0.19
Sift	Benign	0.13	T;T
Sift4G	Benign	0.21	T;T
Polyphen		0.0	B;B
Vest4		0.28
MVP		0.26
MPC		2.4
ClinPred		0.0012	T
GERP RS		-1.4
Varity_R		0.20
gMVP		0.14
Mutation Taster		=99/1	polymorphism

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: rs382627; hg19: chr1-161487805; COSMIC: COSV54837235;