1-161673254-A-G

Position:

• chr1-161673254-A-G

Variant summary

Our verdict is Benign. Variant got -12 ACMG points: 0P and 12B. BP4_Strong BA1

The NM_001394477.1(FCGR2B):​c.646+25A>G variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.369 in 1,278,496 control chromosomes in the GnomAD database, including 129,070 homozygotes. In-silico tool predicts a benign outcome for this variant. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar.

• Frequency:
  • Genomes: 𝑓 0.43 (12986 hom., cov: 28)
  • Exomes 𝑓: 0.36 (116084 hom.)
• Consequence: FCGR2B NM_001394477.1 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 0.0410

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]

FCGR2B (HGNC:):

ACMG classification

Verdict is Benign. Variant got -12 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.92).
• BA1: GnomAd4 highest subpopulation (AMR) allele frequency at 95% confidence interval = 0.543 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
FCGR2B	NM_001394477.1	c.646+25A>G		intron_variant		ENST00000358671.10	NP_001381406.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
FCGR2B	ENST00000358671.10	c.646+25A>G		intron_variant		1	NM_001394477.1	ENSP00000351497.5

Frequencies

GnomAD3 genomes AF: 0.435 AC: 58613 AN: 134756 Hom.: 12968 Cov.: 28

Gnomad AFR AF: 0.352

Gnomad AMI AF: 0.475

Gnomad AMR AF: 0.553

Gnomad ASJ AF: 0.381

Gnomad EAS AF: 0.517

Gnomad SAS AF: 0.489

Gnomad FIN AF: 0.421

Gnomad MID AF: 0.433

Gnomad NFE AF: 0.451

Gnomad OTH AF: 0.437

GnomAD3 exomes AF: 0.197 AC: 33536 AN: 169886 Hom.: 8854 AF XY: 0.183 AC XY: 16720 AN XY: 91386

Gnomad AFR exome AF: 0.164

Gnomad AMR exome AF: 0.380

Gnomad ASJ exome AF: 0.0880

Gnomad EAS exome AF: 0.341

Gnomad SAS exome AF: 0.165

Gnomad FIN exome AF: 0.171

Gnomad NFE exome AF: 0.154

Gnomad OTH exome AF: 0.215

GnomAD4 exome AF: 0.361 AC: 412601 AN: 1143648 Hom.: 116084 Cov.: 40 AF XY: 0.361 AC XY: 205545 AN XY: 569492

Gnomad4 AFR exome AF: 0.246

Gnomad4 AMR exome AF: 0.498

Gnomad4 ASJ exome AF: 0.291

Gnomad4 EAS exome AF: 0.456

Gnomad4 SAS exome AF: 0.407

Gnomad4 FIN exome AF: 0.386

Gnomad4 NFE exome AF: 0.351

Gnomad4 OTH exome AF: 0.378

GnomAD4 genome AF: 0.435 AC: 58657 AN: 134848 Hom.: 12986 Cov.: 28 AF XY: 0.437 AC XY: 28635 AN XY: 65514

Gnomad4 AFR AF: 0.352

Gnomad4 AMR AF: 0.554

Gnomad4 ASJ AF: 0.381

Gnomad4 EAS AF: 0.517

Gnomad4 SAS AF: 0.489

Gnomad4 FIN AF: 0.421

Gnomad4 NFE AF: 0.451

Gnomad4 OTH AF: 0.440

Alfa AF: 0.448 Hom.: 1778

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.92
CADD	Benign	1.6
DANN	Benign	0.32

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: rs2125685; hg19: chr1-161643044; COSMIC: COSV52681008; COSMIC: COSV52681008;