Genetic Variant NM_001136219.3:c.645A>G (chr1-161510859-A-G) – ACMG Classification: Benign (-21 pts)

Variant summary

Our verdict is Benign. The variant received -21 ACMG points: 0P and 21B. BP4_StrongBP6_Very_StrongBP7BA1

The NM_001136219.3(FCGR2A):c.645A>G(p.Pro215Pro) variant causes a synonymous change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.111 in 1,614,006 control chromosomes in the GnomAD database, including 11,351 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★★).

Frequency

Genomes: 𝑓 0.088 ( 869 hom., cov: 33)

Exomes 𝑓: 0.11 ( 10482 hom. )

Consequence

FCGR2A
NM_001136219.3 synonymous

Scores

Clinical Significance

Benign criteria provided, multiple submitters, no conflicts B:2

Conservation

PhyloP100: -0.233

Publications

23 publications found

Variant links:

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]

FCGR2A links:

ENSG00000294554 (HGNC:):

ENSG00000294554 links:

Genome browser will be placed here

ACMG classification

Classification was made for transcript

Our verdict: Benign. The variant received -21 ACMG points.

BP4

Computational evidence support a benign effect (BayesDel_noAF=-0.94).

BP6

Variant 1-161510859-A-G is Benign according to our data. Variant chr1-161510859-A-G is described in ClinVar as Benign. ClinVar VariationId is 402854.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars.

BP7

Synonymous conserved (PhyloP=-0.233 with no splicing effect.

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 rank	MANE	Protein	UniProt
FCGR2A	NM_001136219.3 link	c.645A>G	p.Pro215Pro	synonymous_variant	Exon 5 of 7	ENST00000271450.12	NP_001129691.1	P12318-1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
FCGR2A	ENST00000271450.12 link	c.645A>G	p.Pro215Pro	synonymous_variant	Exon 5 of 7	1	NM_001136219.3	ENSP00000271450.6		P12318-1

Frequencies

GnomAD3 genomes

AF:

0.0883

AC:

13434

AN:

152092

Hom.:

869

Cov.:

show subpopulations

Gnomad AFR

AF:

0.0213

Gnomad AMI

AF:

0.0779

Gnomad AMR

AF:

0.0988

Gnomad ASJ

AF:

0.244

Gnomad EAS

AF:

0.000770

Gnomad SAS

AF:

0.0853

Gnomad FIN

AF:

0.109

Gnomad MID

AF:

0.149

Gnomad NFE

AF:

0.122

Gnomad OTH

AF:

0.100

GnomAD2 exomes

AF:

0.103

AC:

25952

AN:

251426

AF XY:

0.108

show subpopulations

Gnomad AFR exome

AF:

0.0191

Gnomad AMR exome

AF:

0.0643

Gnomad ASJ exome

AF:

0.248

Gnomad EAS exome

AF:

0.000381

Gnomad FIN exome

AF:

0.119

Gnomad NFE exome

AF:

0.130

Gnomad OTH exome

AF:

0.131

GnomAD4 exome

AF:

0.114

AC:

166188

AN:

1461796

Hom.:

10482

Cov.:

AF XY:

0.114

AC XY:

83244

AN XY:

727202

show subpopulations

African (AFR)

AF:

0.0183

AC:

611

AN:

33478

American (AMR)

AF:

0.0672

AC:

3006

AN:

44720

Ashkenazi Jewish (ASJ)

AF:

0.251

AC:

6568

AN:

26128

East Asian (EAS)

AF:

0.000176

AC:

AN:

39668

South Asian (SAS)

AF:

0.0920

AC:

7938

AN:

86258

European-Finnish (FIN)

AF:

0.115

AC:

6134

AN:

53420

Middle Eastern (MID)

AF:

0.191

AC:

1104

AN:

5766

European-Non Finnish (NFE)

AF:

0.121

AC:

134098

AN:

1111970

Other (OTH)

AF:

0.111

AC:

6722

AN:

60388

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.512

Heterozygous variant carriers

9874

19748

29622

39496

49370

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Exome Het

Exome Hom

Variant carriers

4676

9352

14028

18704

23380

<30

30-35

35-40

40-45

45-50

50-55

55-60

60-65

65-70

70-75

75-80

>80

Age

GnomAD4 genome

AF:

0.0882

AC:

13428

AN:

152210

Hom.:

869

Cov.:

AF XY:

0.0890

AC XY:

6621

AN XY:

74420

show subpopulations

African (AFR)

AF:

0.0212

AC:

881

AN:

41542

American (AMR)

AF:

0.0986

AC:

1508

AN:

15290

Ashkenazi Jewish (ASJ)

AF:

0.244

AC:

848

AN:

3472

East Asian (EAS)

AF:

0.000772

AC:

AN:

5180

South Asian (SAS)

AF:

0.0854

AC:

412

AN:

4824

European-Finnish (FIN)

AF:

0.109

AC:

1160

AN:

10594

Middle Eastern (MID)

AF:

0.143

AC:

AN:

294

European-Non Finnish (NFE)

AF:

0.122

AC:

8291

AN:

67990

Other (OTH)

AF:

0.0999

AC:

211

AN:

2112

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.507

Heterozygous variant carriers

639

1278

1916

2555

3194

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Genome Het

Genome Hom

Variant carriers

152

304

456

608

760

<30

30-35

35-40

40-45

45-50

50-55

55-60

60-65

65-70

70-75

75-80

>80

Age

Alfa

AF:

0.124

Hom.:

740

Bravo

AF:

0.0867

Asia WGS

AF:

0.0290

AC:

105

AN:

3478

EpiCase

AF:

0.142

EpiControl

AF:

0.147

ClinVar

Significance: Benign

Submissions summary: Benign:2

Revision: criteria provided, multiple submitters, no conflicts

LINK: link

Submissions by phenotype

not specified

Benign:1

Mar 28, 2016

Laboratory for Molecular Medicine, Mass General Brigham Personalized Medicine

Significance:Benign

Review Status:criteria provided, single submitter

Collection Method:clinical testing

Variant identified in a genome or exome case(s) and assessed due to predicted null impact of the variant or pathogenic assertions in the literature or databases. Disclaimer: This variant has not undergone full assessment. The following are preliminary notes: Frequency -

not provided

Benign:1

Breakthrough Genomics, Breakthrough Genomics

Significance:Benign

Review Status:criteria provided, single submitter

Collection Method:not provided

- -

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

AlphaMissense

Benign

0.086

BayesDel_noAF

Benign

-0.94

CADD

Benign

1.2

(source)

DANN

Benign

0.39

PhyloP100

-0.23

RBP_binding_hub_radar

0.0

RBP_regulation_power_radar

1.1

Mutation Taster

=100/0

polymorphism (auto)

(source)

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

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Variant summary

Frequency

Consequence

Scores

Clinical Significance

Conservation

Publications

ACMG classification

Transcripts

RefSeq

Ensembl

Frequencies

Age Distribution

Age Distribution

ClinVar

Submissions by phenotype

Computational scores

Splicing

Publications

Other links and lift over