rs145342974

Variant names:

Your query was ambiguous. Multiple possible variants found:

Variant summary

Our verdict is Likely benign. The variant received -2 ACMG points: 2P and 4B. PM2BP4_Strong

The NM_000566.4(FCGR1A):c.940C>G(p.Arg314Gly) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00000943 in 1,590,128 control chromosomes in the GnomAD database, including 1 homozygotes. In-silico tool predicts a benign outcome for this variant. 16/22 in silico tools predict a benign outcome for this variant. Variant has been reported in ClinVar as Uncertain significance (★). Another variant affecting the same amino acid position, but resulting in a different missense (i.e. R314C) has been classified as Uncertain significance.

Frequency

Genomes: 𝑓 0.000048 ( 0 hom., cov: 26)

Exomes 𝑓: 0.0000055 ( 1 hom. )

Consequence

FCGR1A
NM_000566.4 missense

Scores

Clinical Significance

Uncertain significance criteria provided, single submitter U:1

Conservation

PhyloP100: -1.44

Publications

2 publications found

Variant links:

Genes affected

FCGR1A (HGNC:3613): (Fc gamma receptor Ia) This gene encodes a protein that plays an important role in the immune response. This protein is a high-affinity Fc-gamma receptor. The gene is one of three related gene family members located on chromosome 1. [provided by RefSeq, Jul 2008]

FCGR1A links:

ENSG00000233030 (HGNC:):

ENSG00000233030 links:

H2BC18 (HGNC:24700): (H2B clustered histone 18) Histones are basic nuclear proteins that are responsible for the nucleosome structure of the chromosomal fiber in eukaryotes. This structure consists of approximately 146 bp of DNA wrapped around a nucleosome, an octamer composed of pairs of each of the four core histones (H2A, H2B, H3, and H4). The chromatin fiber is further compacted through the interaction of a linker histone, H1, with the DNA between the nucleosomes to form higher order chromatin structures. This gene encodes a replication-dependent histone that is a member of the histone H2B family and is found in a histone cluster on chromosome 1. [provided by RefSeq, Aug 2015]

H2BC18 links:

Genome browser will be placed here

ACMG classification

Classification was made for transcript

Our verdict: Likely_benign. The variant received -2 ACMG points.

PM2

Very rare variant in population databases, with high coverage;

BP4

Computational evidence support a benign effect (MetaRNN=0.057468414).

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_000566.4. You can select a different transcript below to see updated ACMG assignments.

RefSeq Transcripts

Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
FCGR1A	NM_000566.4	MANE Select	c.940C>G	p.Arg314Gly	missense	Exon 6 of 6	NP_000557.1	P12314-1
FCGR1A	NM_001378804.1		c.943C>G	p.Arg315Gly	missense	Exon 6 of 6	NP_001365733.1
FCGR1A	NM_001378805.1		c.919C>G	p.Arg307Gly	missense	Exon 5 of 5	NP_001365734.1

Ensembl Transcripts

Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
FCGR1A	ENST00000369168.5	TSL:1 MANE Select	c.940C>G	p.Arg314Gly	missense	Exon 6 of 6	ENSP00000358165.4	P12314-1
ENSG00000233030	ENST00000428289.1	TSL:1	n.1063+626G>C		intron	N/A
FCGR1A	ENST00000964516.1		c.1030C>G	p.Arg344Gly	missense	Exon 7 of 7	ENSP00000634575.1

Frequencies

GnomAD3 genomes

AF:

0.0000480

AC:

AN:

145696

Hom.:

Cov.:

show subpopulations

Gnomad AFR

AF:

0.000132

Gnomad AMI

AF:

0.00

Gnomad AMR

AF:

0.0000676

Gnomad ASJ

AF:

0.00

Gnomad EAS

AF:

0.00

Gnomad SAS

AF:

0.00

Gnomad FIN

AF:

0.00

Gnomad MID

AF:

0.00

Gnomad NFE

AF:

0.0000150

Gnomad OTH

AF:

0.00

GnomAD2 exomes

AF:

0.0000285

AC:

AN:

245996

AF XY:

0.00

show subpopulations

Gnomad AFR exome

AF:

0.000471

Gnomad AMR exome

AF:

0.00

Gnomad ASJ exome

AF:

0.00

Gnomad EAS exome

AF:

0.00

Gnomad FIN exome

AF:

0.00

Gnomad NFE exome

AF:

0.00

Gnomad OTH exome

AF:

0.00

GnomAD4 exome

AF:

0.00000554

AC:

AN:

1444338

Hom.:

Cov.:

AF XY:

0.00000278

AC XY:

AN XY:

718646

show subpopulations

African (AFR)

AF:

0.000123

AC:

AN:

32508

American (AMR)

AF:

0.00

AC:

AN:

44484

Ashkenazi Jewish (ASJ)

AF:

0.00

AC:

AN:

25548

East Asian (EAS)

AF:

0.00

AC:

AN:

39186

South Asian (SAS)

AF:

0.00

AC:

AN:

85322

European-Finnish (FIN)

AF:

0.00

AC:

AN:

53172

Middle Eastern (MID)

AF:

0.00

AC:

AN:

4072

European-Non Finnish (NFE)

AF:

0.00000273

AC:

AN:

1100560

Other (OTH)

AF:

0.0000168

AC:

AN:

59486

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.600

Heterozygous variant carriers

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Exome Het

Exome Hom

Variant carriers

<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:

0.0000480

AC:

AN:

145790

Hom.:

Cov.:

AF XY:

0.0000281

AC XY:

AN XY:

71186

show subpopulations

African (AFR)

AF:

0.000131

AC:

AN:

38084

American (AMR)

AF:

0.0000675

AC:

AN:

14816

Ashkenazi Jewish (ASJ)

AF:

0.00

AC:

AN:

3274

East Asian (EAS)

AF:

0.00

AC:

AN:

5026

South Asian (SAS)

AF:

0.00

AC:

AN:

4614

European-Finnish (FIN)

AF:

0.00

AC:

AN:

10164

Middle Eastern (MID)

AF:

0.00

AC:

AN:

288

European-Non Finnish (NFE)

AF:

0.0000150

AC:

AN:

66632

Other (OTH)

AF:

0.00

AC:

AN:

2012

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.539

Heterozygous variant carriers

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Genome Het

Variant carriers

<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:

0.00

Hom.:

Bravo

AF:

0.0000529

ESP6500AA

AF:

0.000944

AC:

ESP6500EA

AF:

0.00

AC:

ExAC

AF:

0.0000501

AC:

ClinVar

ClinVar submissions

Significance:Uncertain significance

Revision:criteria provided, single submitter

View on ClinVar

Pathogenic

VUS

Benign

Condition

not specified (1)

Computational scores

Source: dbNSFP v4.9

Name

Calibrated prediction

Score

Prediction

AlphaMissense

Benign

0.11

BayesDel_addAF

Benign

-0.45

BayesDel_noAF

Benign

-0.57

CADD

Benign

5.7

(source)

DANN

Benign

0.83

DEOGEN2

Benign

0.021

Eigen

Benign

-0.83

Eigen_PC

Benign

-0.91

FATHMM_MKL

Benign

0.019

LIST_S2

Benign

0.47

M_CAP

Benign

0.0037

MetaRNN

Benign

0.057

MetaSVM

Benign

-0.95

MutationAssessor

Benign

1.1

PhyloP100

-1.4

PrimateAI

Benign

0.24

PROVEAN

Benign

-1.1

REVEL

Benign

0.065

Sift

Benign

0.19

Sift4G

Benign

0.29

Polyphen

0.34

Vest4

0.12

MVP

0.34

ClinPred

0.057

GERP RS

1.1

Varity_R

0.065

gMVP

0.11

Mutation Taster

=98/2

polymorphism

(source)

Splicing

Name

Calibrated prediction

Score

Prediction

SpliceAI score (max)

0.10

Details are displayed if max score is > 0.2

Find out detailed SpliceAI scores and Pangolin per-transcript scores at spliceailookup.broadinstitute.org

Publications

You must be logged in to view publications. This limit was set because tens of millions (!) of queries from AI bots are generated daily.

Variant summary

Frequency

Consequence

Scores

Clinical Significance

Conservation

Publications

ACMG classification

Variant Effect in Transcripts

RefSeq Transcripts

Ensembl Transcripts

Frequencies

Age Distribution

Age Distribution

ClinVar

Computational scores

Splicing

Publications

Other links and lift over