1-149790164-C-T

Variant names:

• chr1-149790164-C-T
• rs1338887
• NM_000566.4:c.670C>T

Variant summary

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

The NM_000566.4(FCGR1A):​c.670C>T​(p.Gln224*) variant causes a stop gained change involving the alteration of a non-conserved nucleotide. The variant was absent in control chromosomes in GnomAD project. In-silico tool predicts a pathogenic outcome for this variant. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar. Variant results in nonsense mediated mRNA decay.

• Frequency: Genomes: not found (cov: 31)
• Consequence: FCGR1A NM_000566.4 stop_gained
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.351
• Publications: 4 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 2 ACMG points.

• PM2: Very rare variant in population databases, with high coverage

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.670C>T	p.Gln224*	stop_gained	Exon 5 of 6	NP_000557.1	P12314-1
	FCGR1A	NM_001378804.1		c.673C>T	p.Gln225*	stop_gained	Exon 5 of 6	NP_001365733.1
	FCGR1A	NM_001378805.1		c.649C>T	p.Gln217*	stop_gained	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.670C>T	p.Gln224*	stop_gained	Exon 5 of 6	ENSP00000358165.4	P12314-1
	ENSG00000233030	ENST00000428289.1	TSL:1	n.1063+1794G>A		intron	N/A
	FCGR1A	ENST00000964516.1		c.760C>T	p.Gln254*	stop_gained	Exon 6 of 7	ENSP00000634575.1

Frequencies

GnomAD3 genomes Cov.: 31

GnomAD4 exome Cov.: 32

GnomAD4 genome Cov.: 31

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_addAF	Pathogenic	0.56	D
BayesDel_noAF	Pathogenic	0.29
CADD	Pathogenic	33
DANN	Uncertain	0.99
Eigen	Benign	0.17
Eigen_PC	Benign	-0.19
FATHMM_MKL	Benign	0.025	N
PhyloP100		-0.35
Vest4		0.56
GERP RS		2.5
Mutation Taster		=23/177	disease causing (fs/PTC)

Splicing

Name	Calibrated prediction	Score	Prediction
SpliceAI score (max)		0.12		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: rs1338887; hg19: chr1-149761720;