chr1-161648361-T-C

Variant names:

• chr1-161648361-T-C
• rs6674499
• NM_004001.5:c.-73+1100T>C

Variant summary

Our verdict is Benign. The variant received -12 ACMG points: 0P and 12B. BP4_Strong BA1

The NM_004001.5(FCGR2B):​c.-73+1100T>C variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.109 in 146,288 control chromosomes in the GnomAD database, including 1,012 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 0.11 (1012 hom., cov: 28)
• Consequence: FCGR2B NM_004001.5 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 0.289
• Publications: 5 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

ENSG00000301529 (HGNC:):

ACMG classification

Our verdict: Benign. The variant received -12 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.95).
• BA1: GnomAd4 highest subpopulation (AMR) allele frequency at 95% confidence interval = 0.145 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
FCGR2B	NM_004001.5	c.-73+1100T>C		intron_variant	Intron 1 of 8		NP_003992.3
FCGR2B	NM_001002275.3	c.-73+1100T>C		intron_variant	Intron 1 of 8		NP_001002275.1
FCGR2B	NM_001190828.2	c.-73+1100T>C		intron_variant	Intron 1 of 7		NP_001177757.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
ENSG00000301529	ENST00000779503.1	n.179-354T>C		intron_variant	Intron 2 of 2
ENSG00000301529	ENST00000779504.1	n.227-424T>C		intron_variant	Intron 2 of 2
ENSG00000301529	ENST00000779505.1	n.230-354T>C		intron_variant	Intron 2 of 2

Frequencies

GnomAD3 genomes AF: 0.109 AC: 16001 AN: 146170 Hom.: 1013 Cov.: 28

Gnomad AFR AF: 0.0467

Gnomad AMI AF: 0.0571

Gnomad AMR AF: 0.150

Gnomad ASJ AF: 0.187

Gnomad EAS AF: 0.0894

Gnomad SAS AF: 0.0600

Gnomad FIN AF: 0.137

Gnomad MID AF: 0.143

Gnomad NFE AF: 0.135

Gnomad OTH AF: 0.120

We have no GnomAD4 exomes data on this position. Probably position not covered by the project.

GnomAD4 genome AF: 0.109 AC: 15993 AN: 146288 Hom.: 1012 Cov.: 28 AF XY: 0.110 AC XY: 7840 AN XY: 71098

African (AFR) AF: 0.0465 AC: 1832 AN: 39356

American (AMR) AF: 0.150 AC: 2160 AN: 14360

Ashkenazi Jewish (ASJ) AF: 0.187 AC: 636 AN: 3400

East Asian (EAS) AF: 0.0890 AC: 449 AN: 5044

South Asian (SAS) AF: 0.0591 AC: 267 AN: 4516

European-Finnish (FIN) AF: 0.137 AC: 1355 AN: 9880

Middle Eastern (MID) AF: 0.136 AC: 39 AN: 286

European-Non Finnish (NFE) AF: 0.135 AC: 8962 AN: 66542

Other (OTH) AF: 0.121 AC: 241 AN: 1994

Alfa AF: 0.113 Hom.: 133

Bravo AF: 0.116

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.95
CADD	Benign	8.8
DANN	Benign	0.76
PhyloP100		0.29
Mutation Taster		=100/0	polymorphism (auto)

Splicing

Find out detailed SpliceAI scores and Pangolin per-transcript scores at spliceailookup.broadinstitute.org

Other links and lift over

dbSNP: rs6674499; hg19: chr1-161618151;