rs1050208

Variant names:

• chr1-149791405-T-C
• rs1050208
• NM_000566.4:c.1013T>C

Variant summary

Our verdict is Benign. The variant received -16 ACMG points: 0P and 16B. BP4_Strong BP6_Very_Strong BS2

The NM_000566.4(FCGR1A):​c.1013T>C​(p.Ile338Thr) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00424 in 1,599,558 control chromosomes in the GnomAD database, including 326 homozygotes. In-silico tool predicts a benign outcome for this variant. 15/21 in silico tools predict a benign outcome for this variant. Variant has been reported in ClinVar as Likely benign (★★).

• Frequency:
  • Genomes: 𝑓 0.0036 (20 hom., cov: 26)
  • Exomes 𝑓: 0.0043 (306 hom.)
• Consequence: FCGR1A NM_000566.4 missense
• Clinical Significance: Likely benign criteria provided, multiple submitters, no conflicts B:4
• Conservation: PhyloP100: -0.282
• Publications: 5 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: Benign. The variant received -16 ACMG points.

• BP4: Computational evidence support a benign effect (MetaRNN=0.0051913857).
• BP6: Variant 1-149791405-T-C is Benign according to our data. Variant chr1-149791405-T-C is described in ClinVar as Likely_benign. ClinVar VariationId is 1285171.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars.
• BS2: High Homozygotes in GnomAd4 at 20 gene

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.1013T>C	p.Ile338Thr	missense	Exon 6 of 6	NP_000557.1	P12314-1
	FCGR1A	NM_001378804.1		c.1016T>C	p.Ile339Thr	missense	Exon 6 of 6	NP_001365733.1
	FCGR1A	NM_001378805.1		c.992T>C	p.Ile331Thr	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.1013T>C	p.Ile338Thr	missense	Exon 6 of 6	ENSP00000358165.4	P12314-1
	ENSG00000233030	ENST00000428289.1	TSL:1	n.1063+553A>G		intron	N/A
	FCGR1A	ENST00000964516.1		c.1103T>C	p.Ile368Thr	missense	Exon 7 of 7	ENSP00000634575.1

Frequencies

GnomAD3 genomes AF: 0.00357 AC: 523 AN: 146444 Hom.: 20 Cov.: 26

Gnomad AFR AF: 0.000992

Gnomad AMI AF: 0.00

Gnomad AMR AF: 0.00289

Gnomad ASJ AF: 0.00879

Gnomad EAS AF: 0.000200

Gnomad SAS AF: 0.00

Gnomad FIN AF: 0.00661

Gnomad MID AF: 0.00

Gnomad NFE AF: 0.00504

Gnomad OTH AF: 0.00351

GnomAD2 exomes AF: 0.00418 AC: 1019 AN: 244050 AF XY: 0.00409

Gnomad AFR exome AF: 0.00155

Gnomad AMR exome AF: 0.00202

Gnomad ASJ exome AF: 0.00820

Gnomad EAS exome AF: 0.0000557

Gnomad FIN exome AF: 0.00954

Gnomad NFE exome AF: 0.00543

Gnomad OTH exome AF: 0.00556

GnomAD4 exome AF: 0.00431 AC: 6264 AN: 1453008 Hom.: 306 Cov.: 31 AF XY: 0.00422 AC XY: 3051 AN XY: 722794

African (AFR) AF: 0.000908 AC: 30 AN: 33030

American (AMR) AF: 0.00220 AC: 98 AN: 44504

Ashkenazi Jewish (ASJ) AF: 0.00831 AC: 214 AN: 25758

East Asian (EAS) AF: 0.00 AC: 0 AN: 39238

South Asian (SAS) AF: 0.000479 AC: 41 AN: 85538

European-Finnish (FIN) AF: 0.00899 AC: 479 AN: 53278

Middle Eastern (MID) AF: 0.00147 AC: 6 AN: 4086

European-Non Finnish (NFE) AF: 0.00462 AC: 5122 AN: 1107792

Other (OTH) AF: 0.00458 AC: 274 AN: 59784

GnomAD4 genome AF: 0.00357 AC: 523 AN: 146550 Hom.: 20 Cov.: 26 AF XY: 0.00322 AC XY: 231 AN XY: 71638

African (AFR) AF: 0.000989 AC: 38 AN: 38414

American (AMR) AF: 0.00289 AC: 43 AN: 14892

Ashkenazi Jewish (ASJ) AF: 0.00879 AC: 29 AN: 3298

East Asian (EAS) AF: 0.000200 AC: 1 AN: 5002

South Asian (SAS) AF: 0.00 AC: 0 AN: 4620

European-Finnish (FIN) AF: 0.00661 AC: 68 AN: 10282

Middle Eastern (MID) AF: 0.00 AC: 0 AN: 288

European-Non Finnish (NFE) AF: 0.00504 AC: 337 AN: 66850

Other (OTH) AF: 0.00347 AC: 7 AN: 2016

Alfa AF: 0.00448 Hom.: 9

Bravo AF: 0.00333

ESP6500AA AF: 0.000710 AC: 3

ESP6500EA AF: 0.00554 AC: 47

ExAC AF: 0.00433 AC: 510

ClinVar

ClinVar submissions as Germline

Significance: Likely benign

Revision: criteria provided, multiple submitters, no conflicts

Pathogenic	VUS	Benign	Condition
-	-	3	not provided (3)
-	-	1	not specified (1)

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
AlphaMissense	Benign	0.076
BayesDel_addAF	Benign	-0.61	T
BayesDel_noAF	Benign	-0.80
CADD	Benign	0.17
DANN	Benign	0.66
DEOGEN2	Benign	0.051	T
Eigen	Benign	-1.4
Eigen_PC	Benign	-1.4
FATHMM_MKL	Benign	0.00035	N
LIST_S2	Benign	0.56	T
MetaRNN	Benign	0.0052	T
MetaSVM	Benign	-0.92	T
MutationAssessor	Benign	-1.6	N
PhyloP100		-0.28
PrimateAI	Benign	0.37	T
PROVEAN	Benign	0.96	N
REVEL	Benign	0.031
Sift	Benign	1.0	T
Sift4G	Benign	1.0	T
Polyphen		0.0	B
Vest4		0.011
MVP		0.082
ClinPred		0.0014	T
GERP RS		-1.0
Varity_R		0.033
gMVP		0.028
Mutation Taster		=100/0	polymorphism (auto)

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: rs1050208; hg19: chr1-149762961;