1-161630041-G-T

Variant summary

Our verdict is Benign. Variant got -9 ACMG points: 0P and 9B. BP4_Strong BP6 BS2

The NM_001244753.2(FCGR3B):c.62-6C>A variant causes a splice region, splice polypyrimidine tract, intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00024 in 1,440,384 control chromosomes in the GnomAD database, including 43 homozygotes. In-silico tool predicts a benign outcome for this variant. 3/3 splice prediction tools predict no significant impact on normal splicing. Variant has been reported in ClinVar as Likely benign (no stars).

• Frequency:
  • Genomes: 𝑓 0.00028 (4 hom., cov: 17)
  • Exomes 𝑓: 0.00024 (39 hom.)
• Consequence: FCGR3B NM_001244753.2 splice_region, splice_polypyrimidine_tract, intron
• Scores: Splicing: ADA: 0.1198
• Clinical Significance: Likely benign no assertion criteria provided B:2
• Conservation: PhyloP100: 0.389

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 -9 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.84).
• BP6: Variant 1-161630041-G-T is Benign according to our data. Variant chr1-161630041-G-T is described in ClinVar as [Likely_benign]. Clinvar id is 1206338.Status of the report is no_assertion_criteria_provided, 0 stars.
• BS2: High Homozygotes in GnomAd at 4 AR gene

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
FCGR3B	NM_001244753.2	c.62-6C>A		splice_region_variant, splice_polypyrimidine_tract_variant, intron_variant		ENST00000650385.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
FCGR3B	ENST00000650385.1	c.62-6C>A		splice_region_variant, splice_polypyrimidine_tract_variant, intron_variant			NM_001244753.2	P2

Frequencies

GnomAD3 genomes AF: 0.000285 AC: 34 AN: 119368 Hom.: 4 Cov.: 17

Gnomad AFR AF: 0.0000340

Gnomad AMI AF: 0.00

Gnomad AMR AF: 0.000272

Gnomad ASJ AF: 0.00760

Gnomad EAS AF: 0.00

Gnomad SAS AF: 0.00

Gnomad FIN AF: 0.00

Gnomad MID AF: 0.00

Gnomad NFE AF: 0.0000685

Gnomad OTH AF: 0.00124

GnomAD3 exomes AF: 0.000485 AC: 102 AN: 210380 Hom.: 16 AF XY: 0.000453 AC XY: 52 AN XY: 114756

Gnomad AFR exome AF: 0.00

Gnomad AMR exome AF: 0.000178

Gnomad ASJ exome AF: 0.00691

Gnomad EAS exome AF: 0.00

Gnomad SAS exome AF: 0.000118

Gnomad FIN exome AF: 0.00

Gnomad NFE exome AF: 0.000223

Gnomad OTH exome AF: 0.00132

GnomAD4 exome AF: 0.000235 AC: 311 AN: 1321016 Hom.: 39 Cov.: 32 AF XY: 0.000207 AC XY: 136 AN XY: 656744

Gnomad4 AFR exome AF: 0.00

Gnomad4 AMR exome AF: 0.000154

Gnomad4 ASJ exome AF: 0.00656

Gnomad4 EAS exome AF: 0.00

Gnomad4 SAS exome AF: 0.00

Gnomad4 FIN exome AF: 0.00

Gnomad4 NFE exome AF: 0.0000636

Gnomad4 OTH exome AF: 0.000814

GnomAD4 genome AF: 0.000285 AC: 34 AN: 119368 Hom.: 4 Cov.: 17 AF XY: 0.000313 AC XY: 18 AN XY: 57482

Gnomad4 AFR AF: 0.0000340

Gnomad4 AMR AF: 0.000272

Gnomad4 ASJ AF: 0.00760

Gnomad4 EAS AF: 0.00

Gnomad4 SAS AF: 0.00

Gnomad4 FIN AF: 0.00

Gnomad4 NFE AF: 0.0000685

Gnomad4 OTH AF: 0.00124

Alfa AF: 0.00161 Hom.: 8

ClinVar

Significance: Likely benign

Submissions summary: Benign:2

Revision: no assertion criteria provided

Submissions by phenotype

not provided Benign:2

Likely benign, no assertion criteria provided	clinical testing	Clinical Genetics DNA and cytogenetics Diagnostics Lab, Erasmus MC, Erasmus Medical Center	-	- -
Likely benign, no assertion criteria provided	clinical testing	Laboratory of Diagnostic Genome Analysis, Leiden University Medical Center (LUMC)	-	- -

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.84
Cadd	Benign	11
Dann	Benign	0.86

Splicing

Name	Calibrated prediction	Score	Prediction
dbscSNV1_ADA	Benign	0.12
dbscSNV1_RF	Benign	0.41
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: rs546592367; hg19: chr1-161599831;