1-149791298-G-C

Variant names:

• chr1-149791298-G-C
• rs1346007587
• NM_000566.4:c.906G>C

Variant summary

Our verdict is Likely benign. The variant received -2 ACMG points: 2P and 4B. PM2 BP4_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. 16/22 in silico tools predict a benign outcome for this variant. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar. 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
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -1.14
• Publications: 0 publications found

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]

ENSG00000233030 (HGNC:):

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]

ACMG classification

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=0.060887933).

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

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	FCGR1A	NM_000566.4	MANE Select	c.906G>C	p.Met302Ile	missense	Exon 6 of 6	NP_000557.1	P12314-1
	FCGR1A	NM_001378804.1		c.909G>C	p.Met303Ile	missense	Exon 6 of 6	NP_001365733.1
	FCGR1A	NM_001378805.1		c.885G>C	p.Met295Ile	missense	Exon 5 of 5	NP_001365734.1

Ensembl Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	FCGR1A	ENST00000369168.5	TSL:1 MANE Select	c.906G>C	p.Met302Ile	missense	Exon 6 of 6	ENSP00000358165.4	P12314-1
	ENSG00000233030	ENST00000428289.1	TSL:1	n.1063+660C>G		intron	N/A
	FCGR1A	ENST00000964516.1		c.996G>C	p.Met332Ile	missense	Exon 7 of 7	ENSP00000634575.1

Frequencies

GnomAD3 genomes AF: 0.00000677 AC: 1 AN: 147676 Hom.: 0 Cov.: 26

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.: 31

GnomAD4 genome AF: 0.00000677 AC: 1 AN: 147784 Hom.: 0 Cov.: 26 AF XY: 0.00 AC XY: 0 AN XY: 72092

African (AFR) AF: 0.00 AC: 0 AN: 39512

American (AMR) AF: 0.00 AC: 0 AN: 14884

Ashkenazi Jewish (ASJ) AF: 0.00 AC: 0 AN: 3326

East Asian (EAS) AF: 0.00 AC: 0 AN: 5000

South Asian (SAS) AF: 0.000218 AC: 1 AN: 4590

European-Finnish (FIN) AF: 0.00 AC: 0 AN: 10238

Middle Eastern (MID) AF: 0.00 AC: 0 AN: 290

European-Non Finnish (NFE) AF: 0.00 AC: 0 AN: 67016

Other (OTH) AF: 0.00 AC: 0 AN: 2034

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
AlphaMissense	Benign	0.19
BayesDel_addAF	Benign	-0.31	T
BayesDel_noAF	Benign	-0.69
CADD	Benign	0.0050
DANN	Benign	0.65
DEOGEN2	Benign	0.012	T
Eigen	Benign	-1.4
Eigen_PC	Benign	-1.4
FATHMM_MKL	Benign	0.017	N
LIST_S2	Benign	0.60	T
M_CAP	Benign	0.0022	T
MetaRNN	Benign	0.061	T
MetaSVM	Benign	-0.90	T
MutationAssessor	Benign	0.17	N
PhyloP100		-1.1
PrimateAI	Benign	0.42	T
PROVEAN	Benign	-0.47	N
REVEL	Benign	0.015
Sift	Benign	0.30	T
Sift4G	Benign	0.59	T
Polyphen		0.0010	B
Vest4		0.092
MutPred		0.36		Loss of sheet (P = 0.0126)
MVP		0.43
ClinPred		0.094	T
GERP RS		-2.5
Varity_R		0.058
gMVP		0.13
Mutation Taster		=100/0	polymorphism

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

Other links and lift over

dbSNP: rs1346007587; hg19: chr1-149762854;