1-149790308-C-A

Variant names:

• chr1-149790308-C-A
• rs782448594
• NM_000566.4:c.814C>A

Variant summary

Our verdict is Uncertain significance. The variant received 0 ACMG points: 2P and 2B. PM2 BP4_Moderate

The NM_000566.4(FCGR1A):​c.814C>A​(p.Arg272Ser) 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. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar. Another variant affecting the same amino acid position, but resulting in a different missense (i.e. R272C) has been classified as Uncertain significance.

• Frequency:
  • Genomes: not found (cov: 30)
  • Exomes 𝑓: 7.0e-7 (0 hom.)
  • Failed GnomAD Quality Control
• Consequence: FCGR1A NM_000566.4 missense
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 0.585
• Publications: 1 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: Uncertain_significance. The variant received 0 ACMG points.

• PM2: Very rare variant in population databases, with high coverage
• BP4: Computational evidence support a benign effect (MetaRNN=0.22627822).

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.814C>A	p.Arg272Ser	missense	Exon 5 of 6	NP_000557.1	P12314-1
	FCGR1A	NM_001378804.1		c.817C>A	p.Arg273Ser	missense	Exon 5 of 6	NP_001365733.1
	FCGR1A	NM_001378805.1		c.793C>A	p.Arg265Ser	missense	Exon 4 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.814C>A	p.Arg272Ser	missense	Exon 5 of 6	ENSP00000358165.4	P12314-1
	ENSG00000233030	ENST00000428289.1	TSL:1	n.1063+1650G>T		intron	N/A
	FCGR1A	ENST00000964516.1		c.904C>A	p.Arg302Ser	missense	Exon 6 of 7	ENSP00000634575.1

Frequencies

GnomAD3 genomes Cov.: 30

GnomAD4 exome Data not reliable, filtered out with message: AS_VQSR AF: 6.96e-7 AC: 1 AN: 1436238 Hom.: 0 Cov.: 32 AF XY: 0.00000141 AC XY: 1 AN XY: 711722

⚠️ The allele balance in gnomAD version 4 Exomes is significantly skewed from the expected value of 0.5.

African (AFR) AF: 0.00 AC: 0 AN: 33234

American (AMR) AF: 0.0000248 AC: 1 AN: 40378

Ashkenazi Jewish (ASJ) AF: 0.00 AC: 0 AN: 25486

East Asian (EAS) AF: 0.00 AC: 0 AN: 39210

South Asian (SAS) AF: 0.00 AC: 0 AN: 82812

European-Finnish (FIN) AF: 0.00 AC: 0 AN: 51708

Middle Eastern (MID) AF: 0.00 AC: 0 AN: 4524

European-Non Finnish (NFE) AF: 0.00 AC: 0 AN: 1099418

Other (OTH) AF: 0.00 AC: 0 AN: 59468

⚠️ The allele balance in gnomAD4 Exomes is highly skewed from 0.5 (p-value = 0), which strongly suggests a high chance of mosaicism in these individuals.

GnomAD4 genome Cov.: 30

Alfa AF: 0.00 Hom.: 0

Bravo AF: 0.0000113

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
AlphaMissense	Benign	0.28
BayesDel_addAF	Benign	-0.17	T
BayesDel_noAF	Benign	-0.48
CADD	Uncertain	25
DANN	Uncertain	0.99
DEOGEN2	Benign	0.012	T
Eigen	Benign	0.16
Eigen_PC	Benign	0.042
FATHMM_MKL	Benign	0.66	D
LIST_S2	Benign	0.83	T
M_CAP	Benign	0.0050	T
MetaRNN	Benign	0.23	T
MetaSVM	Benign	-0.97	T
MutationAssessor	Pathogenic	2.9	M
PhyloP100		0.58
PrimateAI	Benign	0.25	T
PROVEAN	Uncertain	-2.6	D
REVEL	Benign	0.16
Sift	Benign	0.13	T
Sift4G	Benign	0.071	T
Polyphen		0.96	D
Vest4		0.21
MutPred		0.36		Gain of disorder (P = 0.0395)
MVP		0.57
ClinPred		0.98	D
GERP RS		1.5
Varity_R		0.37
gMVP		0.32
Mutation Taster		=61/39	polymorphism

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

Other links and lift over

dbSNP: rs782448594; hg19: chr1-149761864;