Genetic Variant NM_000566.4:c.190C>G (chr1-149784140-C-G) – ACMG Classification: Likely_benign (-2 pts)

Variant summary

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

The NM_000566.4(FCGR1A):c.190C>G(p.Gln64Glu) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00000137 in 1,459,700 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. Variant has been reported in ClinVar as Uncertain significance (★).

Frequency

Genomes: not found (cov: 27)

Exomes 𝑓: 0.0000014 ( 0 hom. )

Consequence

FCGR1A
NM_000566.4 missense

Scores

Clinical Significance

Uncertain significance criteria provided, single submitter U:1

Conservation

PhyloP100: 0.0960

Publications

1 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:

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:

LOC124904411 (HGNC:):

LOC124904411 links:

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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=0.06419322).

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.190C>G	p.Gln64Glu	missense	Exon 3 of 6	NP_000557.1	P12314-1
FCGR1A	NM_001378804.1		c.193C>G	p.Gln65Glu	missense	Exon 3 of 6	NP_001365733.1
FCGR1A	NM_001378805.1		c.169C>G	p.Gln57Glu	missense	Exon 2 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.190C>G	p.Gln64Glu	missense	Exon 3 of 6	ENSP00000358165.4	P12314-1
FCGR1A	ENST00000964516.1		c.280C>G	p.Gln94Glu	missense	Exon 4 of 7	ENSP00000634575.1
FCGR1A	ENST00000866776.1		c.193C>G	p.Gln65Glu	missense	Exon 3 of 6	ENSP00000536835.1

Frequencies

GnomAD3 genomes

Cov.:

GnomAD4 exome

AF:

0.00000137

AC:

AN:

1459700

Hom.:

Cov.:

AF XY:

0.00000138

AC XY:

AN XY:

726154

show subpopulations

African (AFR)

AF:

0.00

AC:

AN:

33406

American (AMR)

AF:

0.00

AC:

AN:

44704

Ashkenazi Jewish (ASJ)

AF:

0.00

AC:

AN:

26132

East Asian (EAS)

AF:

0.00

AC:

AN:

39700

South Asian (SAS)

AF:

0.00

AC:

AN:

86164

European-Finnish (FIN)

AF:

0.00

AC:

AN:

53420

Middle Eastern (MID)

AF:

0.00

AC:

AN:

4136

European-Non Finnish (NFE)

AF:

0.00000180

AC:

AN:

1111832

Other (OTH)

AF:

0.00

AC:

AN:

60206

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.425

Heterozygous variant carriers

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

GnomAD4 genome

Cov.:

Alfa

AF:

0.00

Hom.:

Bravo

AF:

0.00000378

EpiCase

AF:

0.0000545

EpiControl

AF:

0.00

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

0.065

BayesDel_addAF

Benign

-0.32

BayesDel_noAF

Benign

-0.69

CADD

Benign

(source)

DANN

Benign

0.83

DEOGEN2

Benign

0.043

Eigen

Benign

-0.95

Eigen_PC

Benign

-0.94

FATHMM_MKL

Benign

0.065

LIST_S2

Benign

0.52

M_CAP

Benign

0.0028

MetaRNN

Benign

0.064

MetaSVM

Benign

-0.92

MutationAssessor

Benign

0.74

PhyloP100

0.096

PrimateAI

Benign

0.26

PROVEAN

Benign

-0.60

REVEL

Benign

0.033

Sift

Benign

0.63

Sift4G

Benign

0.60

Polyphen

0.0

Vest4

0.053

MutPred

0.28

Loss of sheet (P = 0.0817)

MVP

0.56

ClinPred

0.033

GERP RS

1.1

Varity_R

0.18

gMVP

0.12

Mutation Taster

=92/8

polymorphism

(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

Variant Effect in Transcripts

RefSeq Transcripts

Ensembl Transcripts

Frequencies

ClinVar

Computational scores

Splicing

Publications

Other links and lift over