1-161673254-A-G

Variant names:

• chr1-161673254-A-G
• rs2125685
• NM_001394477.1:c.646+25A>G

Variant summary

Our verdict is Benign. The variant received -8 ACMG points: 0P and 8B. BP4_Strong BS2

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
• Publications: 8 publications found

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 Gene-Disease associations (from GenCC):

• systemic lupus erythematosus

  Inheritance: Unknown Classification: SUPPORTIVE, NO_KNOWN Submitted by: Labcorp Genetics (formerly Invitae), Orphanet

ENSG00000234211 (HGNC:):

ACMG classification

Our verdict: Benign. The variant received -8 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.92).
• BS2: High Homozygotes in GnomAd4 at 12986 Unknown gene

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
FCGR2B	NM_001394477.1	c.646+25A>G		intron_variant	Intron 4 of 7	ENST00000358671.10	NP_001381406.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
FCGR2B	ENST00000358671.10	c.646+25A>G		intron_variant	Intron 4 of 7	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

GnomAD2 exomes AF: 0.197 AC: 33536 AN: 169886 AF XY: 0.183

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 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

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

African (AFR) AF: 0.246 AC: 6909 AN: 28102

American (AMR) AF: 0.498 AC: 15814 AN: 31756

Ashkenazi Jewish (ASJ) AF: 0.291 AC: 6231 AN: 21426

East Asian (EAS) AF: 0.456 AC: 16345 AN: 35842

South Asian (SAS) AF: 0.407 AC: 28470 AN: 69972

European-Finnish (FIN) AF: 0.386 AC: 17578 AN: 45496

Middle Eastern (MID) AF: 0.311 AC: 1373 AN: 4412

European-Non Finnish (NFE) AF: 0.351 AC: 301308 AN: 857458

Other (OTH) AF: 0.378 AC: 18573 AN: 49184

⚠️ The allele balance in gnomAD4 Exomes is highly skewed from 0.5 (p-value = 0), which strongly suggests a high chance of mosaicism in these individuals.

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

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

African (AFR) AF: 0.352 AC: 12533 AN: 35602

American (AMR) AF: 0.554 AC: 7480 AN: 13510

Ashkenazi Jewish (ASJ) AF: 0.381 AC: 1192 AN: 3126

East Asian (EAS) AF: 0.517 AC: 2490 AN: 4816

South Asian (SAS) AF: 0.489 AC: 2037 AN: 4168

European-Finnish (FIN) AF: 0.421 AC: 3998 AN: 9494

Middle Eastern (MID) AF: 0.453 AC: 124 AN: 274

European-Non Finnish (NFE) AF: 0.451 AC: 27608 AN: 61206

Other (OTH) AF: 0.440 AC: 819 AN: 1860

⚠️ The allele balance in gnomAD version 4 Genomes is significantly skewed from the expected value of 0.5. (p-value = 0), which strongly suggests a high chance of mosaicism in these individuals.

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
PhyloP100		0.041
Mutation Taster		=100/0	polymorphism (auto)

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

Other links and lift over

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