Genetic Variant NM_000566.4:c.906G>C (chr1-149791298-G-C) – ACMG Classification: Likely_benign (-2 pts)

Variant summary

Our verdict is Likely benign. Variant got -2 ACMG points: 2P and 4B. PM2BP4_Strong

The NM_000566.4(FCGR1A):c.906G>C(p.Met302Ile) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00000677 in 147,784 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a benign outcome for this variant. 15/20 in silico tools predict a benign outcome for this variant. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar. Another nucleotide change resulting in the same amino acid substitution has been previously reported as Likely benign in ClinVar. Another variant affecting the same amino acid position, but resulting in a different missense (i.e. M302T) has been classified as Uncertain significance.

Frequency

Genomes: 𝑓 0.0000068 ( 0 hom., cov: 26)

Consequence

FCGR1A
NM_000566.4 missense

Scores

Clinical Significance

Not reported in ClinVar

Conservation

PhyloP100: -1.14

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:

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ACMG classification

Classification made for transcript

Verdict is Likely_benign. Variant got -2 ACMG points.

PM2

Very rare variant in population databases, with high coverage;

BP4

Computational evidence support a benign effect (MetaRNN=0.060887933).

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
FCGR1A	NM_000566.4 link	c.906G>C	p.Met302Ile	missense_variant	Exon 6 of 6	ENST00000369168.5	NP_000557.1	P12314-1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
FCGR1A	ENST00000369168.5 link	c.906G>C	p.Met302Ile	missense_variant	Exon 6 of 6	1	NM_000566.4	ENSP00000358165.4		P12314-1

Frequencies

GnomAD3 genomes

AF:

0.00000677

AC:

AN:

147676

Hom.:

Cov.:

show subpopulations

Gnomad AFR

AF:

0.00

Gnomad AMI

AF:

0.00

Gnomad AMR

AF:

0.00

Gnomad ASJ

AF:

0.00

Gnomad EAS

AF:

0.00

Gnomad SAS

AF:

0.000218

Gnomad FIN

AF:

0.00

Gnomad MID

AF:

0.00

Gnomad NFE

AF:

0.00

Gnomad OTH

AF:

0.00

GnomAD4 exome

Cov.:

GnomAD4 genome

AF:

0.00000677

AC:

AN:

147784

Hom.:

Cov.:

AF XY:

0.00

AC XY:

AN XY:

72092

show subpopulations

Gnomad4 AFR

AF:

0.00

Gnomad4 AMR

AF:

0.00

Gnomad4 ASJ

AF:

0.00

Gnomad4 EAS

AF:

0.00

Gnomad4 SAS

AF:

0.000218

Gnomad4 FIN

AF:

0.00

Gnomad4 NFE

AF:

0.00

Gnomad4 OTH

AF:

0.00

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

AlphaMissense

Benign

0.19

BayesDel_addAF

Benign

-0.31

BayesDel_noAF

Benign

-0.69

CADD

Benign

0.0050

DANN

Benign

0.65

DEOGEN2

Benign

0.012

T;T

Eigen

Benign

-1.4

Eigen_PC

Benign

-1.4

FATHMM_MKL

Benign

0.017

LIST_S2

Benign

0.60

T;T

M_CAP

Benign

0.0022

MetaRNN

Benign

0.061

T;T

MetaSVM

Benign

-0.90

MutationAssessor

Benign

0.17

.;N

PrimateAI

Benign

0.42

PROVEAN

Benign

-0.47

N;N

REVEL

Benign

0.015

Sift

Benign

0.30

T;T

Sift4G

Benign

0.59

T;T

Polyphen

0.0010

.;B

Vest4

0.092

MutPred

0.36

.;Loss of sheet (P = 0.0126);

MVP

0.43

ClinPred

0.094

GERP RS

-2.5

Varity_R

0.058

gMVP

0.13

Splicing

Name

Calibrated prediction

Score

Prediction

SpliceAI score (max)

0.010

Details are displayed if max score is > 0.2

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

Publications

No publications associated with this variant yet.

Variant summary

Frequency

Consequence

Scores

Clinical Significance

Conservation

ACMG classification

Transcripts

RefSeq

Ensembl

Frequencies

ClinVar

Computational scores

Splicing

Publications

Other links and lift over