1-161629903-T-C

Variant names:

• chr1-161629903-T-C
• rs448740
• NM_001244753.2:c.194A>G

Variant summary

Our verdict is Benign. The variant received -20 ACMG points: 0P and 20B. BP4_Strong BP6_Very_Strong BA1

The NM_001244753.2(FCGR3B):​c.194A>G​(p.Asn65Ser) variant causes a missense change involving the alteration of a non-conserved nucleotide. In-silico tool predicts a benign outcome for this variant. 14/19 in silico tools predict a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★★).

• Frequency:
  • Genomes: 𝑓 0.92 (32445 hom., cov: 11)
  • Exomes 𝑓: 0.70 (337108 hom.)
  • Failed GnomAD Quality Control
• Consequence: FCGR3B NM_001244753.2 missense
• Clinical Significance: Benign criteria provided, multiple submitters, no conflicts B:2
• Conservation: PhyloP100: -4.37
• Publications: 68 publications found

Genes affected

FCGR3B (HGNC:3620): (Fc gamma receptor IIIb) The protein encoded by this gene is a low affinity receptor for the Fc region of gamma immunoglobulins (IgG). The encoded protein acts as a monomer and can bind either monomeric or aggregated IgG. This gene may function to capture immune complexes in the peripheral circulation. Several transcript variants encoding different isoforms have been found for this gene. A highly-similar gene encoding a related protein is also found on chromosome 1. [provided by RefSeq, Aug 2012]

FCGR3B Gene-Disease associations (from GenCC):

• systemic lupus erythematosus

  Inheritance: Unknown Classification: SUPPORTIVE Submitted by: Orphanet

ENSG00000289768 (HGNC:):

ACMG classification

Our verdict: Benign. The variant received -20 ACMG points.

• BP4: Computational evidence support a benign effect (MetaRNN=1.3109584E-6).
• BP6: Variant 1-161629903-T-C is Benign according to our data. Variant chr1-161629903-T-C is described in ClinVar as Benign. ClinVar VariationId is 242685.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars.
• BA1: GnomAd4 highest subpopulation (NFE) allele frequency at 95% confidence interval = 0.94 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
FCGR3B	NM_001244753.2	c.194A>G	p.Asn65Ser	missense_variant	Exon 3 of 5	ENST00000650385.1	NP_001231682.2

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
FCGR3B	ENST00000650385.1	c.194A>G	p.Asn65Ser	missense_variant	Exon 3 of 5		NM_001244753.2	ENSP00000497461.1
ENSG00000289768	ENST00000699402.1	c.40+1152A>G		intron_variant	Intron 1 of 3			ENSP00000514363.1

Frequencies

GnomAD3 genomes AF: 0.923 AC: 68982 AN: 74730 Hom.: 32429 Cov.: 11

Gnomad AFR AF: 0.850

Gnomad AMI AF: 0.920

Gnomad AMR AF: 0.925

Gnomad ASJ AF: 0.960

Gnomad EAS AF: 0.827

Gnomad SAS AF: 0.935

Gnomad FIN AF: 0.984

Gnomad MID AF: 0.919

Gnomad NFE AF: 0.948

Gnomad OTH AF: 0.929

GnomAD2 exomes AF: 0.619 AC: 144438 AN: 233468 AF XY: 0.624

Gnomad AFR exome AF: 0.609

Gnomad AMR exome AF: 0.516

Gnomad ASJ exome AF: 0.744

Gnomad EAS exome AF: 0.398

Gnomad FIN exome AF: 0.639

Gnomad NFE exome AF: 0.672

Gnomad OTH exome AF: 0.668

GnomAD4 exome Data not reliable, filtered out with message: AS_VQSR AF: 0.697 AC: 907130 AN: 1300890 Hom.: 337108 Cov.: 47 AF XY: 0.700 AC XY: 454087 AN XY: 648784

African (AFR) AF: 0.632 AC: 17477 AN: 27638

American (AMR) AF: 0.548 AC: 21646 AN: 39502

Ashkenazi Jewish (ASJ) AF: 0.807 AC: 19151 AN: 23726

East Asian (EAS) AF: 0.583 AC: 16468 AN: 28238

South Asian (SAS) AF: 0.673 AC: 53173 AN: 78960

European-Finnish (FIN) AF: 0.771 AC: 35905 AN: 46564

Middle Eastern (MID) AF: 0.747 AC: 3892 AN: 5212

European-Non Finnish (NFE) AF: 0.703 AC: 701483 AN: 998246

Other (OTH) AF: 0.718 AC: 37935 AN: 52804

GnomAD4 genome AF: 0.923 AC: 69021 AN: 74782 Hom.: 32445 Cov.: 11 AF XY: 0.924 AC XY: 32691 AN XY: 35374

African (AFR) AF: 0.850 AC: 14970 AN: 17612

American (AMR) AF: 0.925 AC: 5486 AN: 5930

Ashkenazi Jewish (ASJ) AF: 0.960 AC: 2178 AN: 2268

East Asian (EAS) AF: 0.827 AC: 1199 AN: 1450

South Asian (SAS) AF: 0.935 AC: 1602 AN: 1714

European-Finnish (FIN) AF: 0.984 AC: 4877 AN: 4954

Middle Eastern (MID) AF: 0.912 AC: 155 AN: 170

European-Non Finnish (NFE) AF: 0.948 AC: 37243 AN: 39266

Other (OTH) AF: 0.926 AC: 945 AN: 1020

Alfa AF: 0.629 Hom.: 8625

ExAC AF: 0.588 AC: 71082

ClinVar

Significance: Benign

Submissions summary: Benign:2

Revision: criteria provided, multiple submitters, no conflicts

Submissions by phenotype

not provided Benign:2

Dec 26, 2017

Labcorp Genetics (formerly Invitae), Labcorp

Significance: Benign

Review Status: criteria provided, single submitter

Collection Method: clinical testing

- -

-

Breakthrough Genomics, Breakthrough Genomics

Significance: Benign

Review Status: criteria provided, single submitter

Collection Method: not provided

- -

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
AlphaMissense	Benign	0.072
BayesDel_addAF	Benign	-0.46	T
BayesDel_noAF	Benign	-0.90
CADD	Benign	0.0020
DANN	Benign	0.79
DEOGEN2	Benign	0.0028	.;.;T;.;.;.;T
Eigen	Benign	-1.3
Eigen_PC	Benign	-1.5
FATHMM_MKL	Benign	0.0010	N
LIST_S2	Benign	0.076	.;.;T;T;T;T;T
MetaRNN	Benign	0.0000013	T;T;T;T;T;T;T
MetaSVM	Benign	-0.93	T
PhyloP100		-4.4
PrimateAI	Benign	0.28	T
PROVEAN	Benign	0.42	.;N;.;.;N;N;N
REVEL	Benign	0.0060
Sift	Benign	0.89	.;T;.;.;T;T;T
Sift4G	Benign	0.97	.;T;T;T;T;T;.
Vest4		0.039, 0.037, 0.031, 0.034
MPC		1.4
ClinPred		0.0091	T
GERP RS		-2.6
gMVP		0.11
Mutation Taster		=98/2	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: rs448740; hg19: chr1-161599693; COSMIC: COSV54208729;