1-161673236-G-A

Variant summary

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

The NM_001394477.1(FCGR2B):c.646+7G>A variant causes a splice region, intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.000325 in 1,590,370 control chromosomes in the GnomAD database, including 6 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 0.00031 (1 hom., cov: 30)
  • Exomes 𝑓: 0.00033 (5 hom.)
• Consequence: FCGR2B NM_001394477.1 splice_region, intron
• Scores: Splicing: ADA: 0.00003317
• Clinical Significance: Likely benign no assertion criteria provided B:2
• Conservation: PhyloP100: -0.0570

Genes affected

FCGR2B (HGNC:3618): (Fc gamma receptor IIb) The protein encoded by this gene is a low affinity receptor for the Fc region of immunoglobulin gamma complexes. The encoded protein is involved in the phagocytosis of immune complexes and in the regulation of antibody production by B-cells. Variations in this gene may increase susceptibilty to systemic lupus erythematosus (SLE). Several transcript variants encoding different isoforms have been found for this gene. [provided by RefSeq, Jun 2010]

(HGNC:):

ACMG classification

Verdict is Benign. Variant got -9 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.83).
• BP6: Variant 1-161673236-G-A is Benign according to our data. Variant chr1-161673236-G-A is described in ClinVar as [Likely_benign]. Clinvar id is 1285216.Status of the report is no_assertion_criteria_provided, 0 stars. Variant chr1-161673236-G-A is described in Lovd as [Likely_benign].
• BS2: High Homozygotes in GnomAdExome at 2 AR gene

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
FCGR2B	NM_001394477.1	c.646+7G>A		splice_region_variant, intron_variant		ENST00000358671.10

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
FCGR2B	ENST00000358671.10	c.646+7G>A		splice_region_variant, intron_variant		1	NM_001394477.1	P4
	ENST00000453111.1	n.198-953C>T		intron_variant, non_coding_transcript_variant		2

Frequencies

GnomAD3 genomes AF: 0.000302 AC: 45 AN: 149024 Hom.: 1 Cov.: 30

Gnomad AFR AF: 0.0000750

Gnomad AMI AF: 0.00

Gnomad AMR AF: 0.000203

Gnomad ASJ AF: 0.00

Gnomad EAS AF: 0.00526

Gnomad SAS AF: 0.000216

Gnomad FIN AF: 0.000193

Gnomad MID AF: 0.00

Gnomad NFE AF: 0.000104

Gnomad OTH AF: 0.000972

GnomAD3 exomes AF: 0.000542 AC: 128 AN: 236230 Hom.: 2 AF XY: 0.000526 AC XY: 67 AN XY: 127376

Gnomad AFR exome AF: 0.0000664

Gnomad AMR exome AF: 0.0000627

Gnomad ASJ exome AF: 0.00

Gnomad EAS exome AF: 0.00558

Gnomad SAS exome AF: 0.0000723

Gnomad FIN exome AF: 0.000241

Gnomad NFE exome AF: 0.000157

Gnomad OTH exome AF: 0.000348

GnomAD4 exome AF: 0.000327 AC: 471 AN: 1441234 Hom.: 5 Cov.: 32 AF XY: 0.000317 AC XY: 227 AN XY: 715600

Gnomad4 AFR exome AF: 0.00

Gnomad4 AMR exome AF: 0.0000709

Gnomad4 ASJ exome AF: 0.00

Gnomad4 EAS exome AF: 0.00801

Gnomad4 SAS exome AF: 0.0000120

Gnomad4 FIN exome AF: 0.000151

Gnomad4 NFE exome AF: 0.0000954

Gnomad4 OTH exome AF: 0.000639

GnomAD4 genome AF: 0.000308 AC: 46 AN: 149136 Hom.: 1 Cov.: 30 AF XY: 0.000275 AC XY: 20 AN XY: 72694

Gnomad4 AFR AF: 0.0000748

Gnomad4 AMR AF: 0.000203

Gnomad4 ASJ AF: 0.00

Gnomad4 EAS AF: 0.00528

Gnomad4 SAS AF: 0.000216

Gnomad4 FIN AF: 0.000193

Gnomad4 NFE AF: 0.000104

Gnomad4 OTH AF: 0.00144

Alfa AF: 0.000219 Hom.: 1

Bravo AF: 0.000257

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	Genome Diagnostics Laboratory, University Medical Center Utrecht	-	- -
Likely benign, no assertion criteria provided	clinical testing	Clinical Genetics DNA and cytogenetics Diagnostics Lab, Erasmus MC, Erasmus Medical Center	-	- -

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.83
Cadd	Benign	11
Dann	Benign	0.69

Splicing

Name	Calibrated prediction	Score	Prediction
dbscSNV1_ADA	Benign	0.000033
dbscSNV1_RF	Benign	0.0040
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: rs377291694; hg19: chr1-161643026;