1-161629781-T-C

Variant names:

• chr1-161629781-T-C
• rs2290834
• NM_001244753.2:c.316A>G

Variant summary

Our verdict is Benign. The variant received -12 ACMG points: 0P and 12B. BP4_Strong BP6_Very_Strong

The NM_001244753.2(FCGR3B):​c.316A>G​(p.Ile106Val) 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 0.017 (4 hom., cov: 9)
  • Exomes 𝑓: 0.24 (50997 hom.)
  • Failed GnomAD Quality Control
• Consequence: FCGR3B NM_001244753.2 missense
• Clinical Significance: Benign criteria provided, multiple submitters, no conflicts B:2
• Conservation: PhyloP100: -6.08
• Publications: 45 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 -12 ACMG points.

• BP4: Computational evidence support a benign effect (MetaRNN=0.005424112).
• BP6: Variant 1-161629781-T-C is Benign according to our data. Variant chr1-161629781-T-C is described in ClinVar as Benign. ClinVar VariationId is 402858.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
FCGR3B	NM_001244753.2	c.316A>G	p.Ile106Val	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.316A>G	p.Ile106Val	missense_variant	Exon 3 of 5		NM_001244753.2	ENSP00000497461.1
ENSG00000289768	ENST00000699402.1	c.40+1274A>G		intron_variant	Intron 1 of 3			ENSP00000514363.1

Frequencies

GnomAD3 genomes AF: 0.0165 AC: 1082 AN: 65610 Hom.: 4 Cov.: 9

Gnomad AFR AF: 0.00925

Gnomad AMI AF: 0.0255

Gnomad AMR AF: 0.0243

Gnomad ASJ AF: 0.00806

Gnomad EAS AF: 0.0797

Gnomad SAS AF: 0.0241

Gnomad FIN AF: 0.00621

Gnomad MID AF: 0.0278

Gnomad NFE AF: 0.0181

Gnomad OTH AF: 0.0239

GnomAD2 exomes AF: 0.267 AC: 51655 AN: 193734 AF XY: 0.272

Gnomad AFR exome AF: 0.154

Gnomad AMR exome AF: 0.388

Gnomad ASJ exome AF: 0.196

Gnomad EAS exome AF: 0.479

Gnomad FIN exome AF: 0.180

Gnomad NFE exome AF: 0.225

Gnomad OTH exome AF: 0.221

GnomAD4 exome Data not reliable, filtered out with message: AS_VQSR AF: 0.239 AC: 288026 AN: 1202724 Hom.: 50997 Cov.: 28 AF XY: 0.233 AC XY: 139154 AN XY: 596090

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

African (AFR) AF: 0.172 AC: 4401 AN: 25652

American (AMR) AF: 0.395 AC: 13972 AN: 35360

Ashkenazi Jewish (ASJ) AF: 0.146 AC: 3207 AN: 21992

East Asian (EAS) AF: 0.285 AC: 6171 AN: 21664

South Asian (SAS) AF: 0.242 AC: 16469 AN: 67928

European-Finnish (FIN) AF: 0.0948 AC: 3776 AN: 39836

Middle Eastern (MID) AF: 0.139 AC: 620 AN: 4462

European-Non Finnish (NFE) AF: 0.245 AC: 229415 AN: 937764

Other (OTH) AF: 0.208 AC: 9995 AN: 48066

⚠️ The allele balance in gnomAD4 Exomes is highly skewed from 0.5 (p-value = 0.000000), which strongly suggests a high chance of mosaicism in these individuals.

GnomAD4 genome Data not reliable, filtered out with message: AS_VQSR AF: 0.0165 AC: 1084 AN: 65648 Hom.: 4 Cov.: 9 AF XY: 0.0151 AC XY: 471 AN XY: 31148

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

African (AFR) AF: 0.00935 AC: 151 AN: 16144

American (AMR) AF: 0.0243 AC: 118 AN: 4854

Ashkenazi Jewish (ASJ) AF: 0.00806 AC: 17 AN: 2108

East Asian (EAS) AF: 0.0787 AC: 84 AN: 1068

South Asian (SAS) AF: 0.0241 AC: 34 AN: 1410

European-Finnish (FIN) AF: 0.00621 AC: 28 AN: 4510

Middle Eastern (MID) AF: 0.0298 AC: 5 AN: 168

European-Non Finnish (NFE) AF: 0.0181 AC: 618 AN: 34224

Other (OTH) AF: 0.0248 AC: 21 AN: 848

⚠️ The allele balance in gnomAD version 4 Genomes is significantly skewed from the expected value of 0.5. (p-value = 0.000000), which strongly suggests a high chance of mosaicism in these individuals.

Alfa AF: 0.271 Hom.: 2316

ExAC AF: 0.349 AC: 42050

ClinVar

Significance: Benign

Submissions summary: Benign:2

Revision: criteria provided, multiple submitters, no conflicts

Submissions by phenotype

not specified Benign:1

Mar 28, 2016

Laboratory for Molecular Medicine, Mass General Brigham Personalized Medicine

Significance: Benign

Review Status: criteria provided, single submitter

Collection Method: clinical testing

Variant identified in a genome or exome case(s) and assessed due to predicted null impact of the variant or pathogenic assertions in the literature or databases. Disclaimer: This variant has not undergone full assessment. The following are preliminary notes: ExAC frequency -

not provided Benign:1

-

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	0.079
BayesDel_addAF	Benign	-0.38	T
BayesDel_noAF	Benign	-0.78
CADD	Benign	0.0010
DANN	Benign	0.46
DEOGEN2	Benign	0.0021	.;.;T;.;.;.;T
Eigen	Benign	-1.5
Eigen_PC	Benign	-1.7
FATHMM_MKL	Benign	0.00071	N
LIST_S2	Benign	0.14	.;.;T;T;T;T;T
MetaRNN	Benign	0.0054	T;T;T;T;T;T;T
MetaSVM	Benign	-1.0	T
PhyloP100		-6.1
PrimateAI	Benign	0.26	T
PROVEAN	Benign	0.22	.;N;.;.;N;N;N
REVEL	Benign	0.010
Sift	Benign	0.58	.;T;.;.;T;T;T
Sift4G	Benign	0.22	.;T;T;T;T;T;.
Vest4		0.080, 0.082, 0.084, 0.032, 0.049
MPC		1.5
ClinPred		0.0052	T
GERP RS		-5.6
gMVP		0.21
Mutation Taster		=93/7	polymorphism (auto)

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: rs2290834; hg19: chr1-161599571; COSMIC: COSV54209014; COSMIC: COSV54209014;