Genetic Variant FCGR1A:p.Gln246Lys (chr1-149790230-C-A) – ACMG Classification: Uncertain_significance (1 pts)

Variant summary

Our verdict is Uncertain significance. The variant received 1 ACMG points: 2P and 1B. PM2BP4

The NM_000566.4(FCGR1A):c.736C>A(p.Gln246Lys) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant was absent in control chromosomes in GnomAD project. In-silico tool predicts a benign outcome for this variant. 15/22 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: not found (cov: 30)

Consequence

FCGR1A
NM_000566.4 missense

Scores

Clinical Significance

Not reported in ClinVar

Conservation

PhyloP100: 1.00

Publications

4 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:

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ACMG classification

Classification was made for transcript

Our verdict: Uncertain_significance. The variant received 1 ACMG points.

PM2

Very rare variant in population databases, with high coverage;

BP4

Computational evidence support a benign effect (MetaRNN=0.28152296).

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.736C>A	p.Gln246Lys	missense	Exon 5 of 6	NP_000557.1	P12314-1
FCGR1A	NM_001378804.1		c.739C>A	p.Gln247Lys	missense	Exon 5 of 6	NP_001365733.1
FCGR1A	NM_001378805.1		c.715C>A	p.Gln239Lys	missense	Exon 4 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.736C>A	p.Gln246Lys	missense	Exon 5 of 6	ENSP00000358165.4	P12314-1
ENSG00000233030	ENST00000428289.1	TSL:1	n.1063+1728G>T		intron	N/A
FCGR1A	ENST00000964516.1		c.826C>A	p.Gln276Lys	missense	Exon 6 of 7	ENSP00000634575.1

Frequencies

GnomAD3 genomes

Cov.:

GnomAD4 exome

Cov.:

GnomAD4 genome

Cov.:

Alfa

AF:

0.00

Hom.:

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name

Calibrated prediction

Score

Prediction

AlphaMissense

Benign

0.093

BayesDel_addAF

Benign

-0.22

BayesDel_noAF

Benign

-0.56

CADD

Benign

(source)

DANN

Benign

0.78

DEOGEN2

Benign

0.011

Eigen

Benign

0.052

Eigen_PC

Benign

0.0092

FATHMM_MKL

Benign

0.59

LIST_S2

Uncertain

0.87

M_CAP

Benign

0.0037

MetaRNN

Benign

0.28

MetaSVM

Benign

-0.87

MutationAssessor

Uncertain

2.4

PhyloP100

1.0

PrimateAI

Benign

0.33

PROVEAN

Benign

-1.4

REVEL

Benign

0.11

Sift

Benign

0.78

Sift4G

Benign

1.0

Polyphen

0.81

Vest4

0.17

MutPred

0.52

Gain of ubiquitination at Q246 (P = 0.0203)

MVP

0.58

ClinPred

0.90

GERP RS

3.4

Varity_R

0.35

gMVP

0.33

Mutation Taster

=71/29

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