1-161629903-T-C

Position:

• chr1-161629903-T-C

Variant summary

Our verdict is Benign. Variant got -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. 13/18 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

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]

ACMG classification

Verdict is Benign. Variant got -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 id is 242685.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars. Variant chr1-161629903-T-C is described in Lovd as [Benign].
• 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/exons	MANE	UniProt
FCGR3B	NM_001244753.2	c.194A>G	p.Asn65Ser	missense_variant	3/5	ENST00000650385.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
FCGR3B	ENST00000650385.1	c.194A>G	p.Asn65Ser	missense_variant	3/5		NM_001244753.2	P2

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

GnomAD3 exomes AF: 0.619 AC: 144438 AN: 233468 Hom.: 48541 AF XY: 0.624 AC XY: 79224 AN XY: 127038

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 SAS exome AF: 0.593

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

Gnomad4 AFR exome AF: 0.632

Gnomad4 AMR exome AF: 0.548

Gnomad4 ASJ exome AF: 0.807

Gnomad4 EAS exome AF: 0.583

Gnomad4 SAS exome AF: 0.673

Gnomad4 FIN exome AF: 0.771

Gnomad4 NFE exome AF: 0.703

Gnomad4 OTH exome AF: 0.718

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

Gnomad4 AFR AF: 0.850

Gnomad4 AMR AF: 0.925

Gnomad4 ASJ AF: 0.960

Gnomad4 EAS AF: 0.827

Gnomad4 SAS AF: 0.935

Gnomad4 FIN AF: 0.984

Gnomad4 NFE AF: 0.948

Gnomad4 OTH AF: 0.926

Alfa AF: 0.658 Hom.: 3968

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

Benign, criteria provided, single submitter	not provided	Breakthrough Genomics, Breakthrough Genomics	-	- -
Benign, criteria provided, single submitter	clinical testing	Labcorp Genetics (formerly Invitae), Labcorp	Dec 26, 2017	- -

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
MutationTaster	Benign	1.0	P;P;P;P;P;P;P;P
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

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

Publications

LitVar

Other links and lift over

dbSNP: rs448740; hg19: chr1-161599693; COSMIC: COSV54208729;