rs11264799

Positions:

• chr1-157700967-C-T

Variant summary

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

The XM_006711145.2(FCRL3):​c.-204G>A variant causes a upstream gene change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.276 in 161,554 control chromosomes in the GnomAD database, including 6,288 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 0.28 (6101 hom., cov: 32)
  • Exomes 𝑓: 0.19 (187 hom.)
• Consequence: FCRL3 XM_006711145.2 upstream_gene
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.849

Genes affected

FCRL3 (HGNC:18506): (Fc receptor like 3) This gene encodes a member of the immunoglobulin receptor superfamily and is one of several Fc receptor-like glycoproteins clustered on the long arm of chromosome 1. The encoded protein contains immunoreceptor-tyrosine activation motifs and immunoreceptor-tyrosine inhibitory motifs in its cytoplasmic domain and may play a role in regulation of the immune system. Mutations in this gene have been associated with rheumatoid arthritis, autoimmune thyroid disease, and systemic lupus erythematosus. Alternative splicing results in multiple transcript variants. [provided by RefSeq, Feb 2016]

ACMG classification

Verdict is Benign. Variant got -12 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.86).
• BA1: GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.347 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
FCRL3	XM_006711145.2	c.-204G>A		upstream_gene_variant			XP_006711208.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt

Frequencies

GnomAD3 genomes AF: 0.281 AC: 42741 AN: 151890 Hom.: 6094 Cov.: 32

Gnomad AFR AF: 0.352

Gnomad AMI AF: 0.270

Gnomad AMR AF: 0.268

Gnomad ASJ AF: 0.261

Gnomad EAS AF: 0.232

Gnomad SAS AF: 0.183

Gnomad FIN AF: 0.237

Gnomad MID AF: 0.351

Gnomad NFE AF: 0.260

Gnomad OTH AF: 0.285

GnomAD4 exome AF: 0.192 AC: 1831 AN: 9546 Hom.: 187 AF XY: 0.194 AC XY: 943 AN XY: 4862

Gnomad4 AFR exome AF: 0.361

Gnomad4 AMR exome AF: 0.185

Gnomad4 ASJ exome AF: 0.157

Gnomad4 EAS exome AF: 0.142

Gnomad4 SAS exome AF: 0.123

Gnomad4 FIN exome AF: 0.129

Gnomad4 NFE exome AF: 0.205

Gnomad4 OTH exome AF: 0.191

GnomAD4 genome AF: 0.281 AC: 42773 AN: 152008 Hom.: 6101 Cov.: 32 AF XY: 0.278 AC XY: 20676 AN XY: 74290

Gnomad4 AFR AF: 0.351

Gnomad4 AMR AF: 0.268

Gnomad4 ASJ AF: 0.261

Gnomad4 EAS AF: 0.232

Gnomad4 SAS AF: 0.183

Gnomad4 FIN AF: 0.237

Gnomad4 NFE AF: 0.260

Gnomad4 OTH AF: 0.290

Alfa AF: 0.270 Hom.: 1947

Bravo AF: 0.289

Asia WGS AF: 0.269 AC: 934 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.86
CADD	Benign	2.6
DANN	Benign	0.72

Splicing

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

Publications

LitVar

Other links and lift over

dbSNP: rs11264799; hg19: chr1-157670757;