rs6691569

Positions:

• chr1-157678308-G-A

Variant summary

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

The NM_052939.4(FCRL3):​c.*402C>T variant causes a 3 prime UTR change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.26 in 1,010,424 control chromosomes in the GnomAD database, including 34,759 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 0.24 (4478 hom., cov: 32)
  • Exomes 𝑓: 0.26 (30281 hom.)
• Consequence: FCRL3 NM_052939.4 3_prime_UTR
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.797

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=-0.92).
• BA1: GnomAd4 highest subpopulation (NFE) allele frequency at 95% confidence interval = 0.263 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
FCRL3	NM_052939.4	c.*402C>T		3_prime_UTR_variant	15/15	ENST00000368184.8	NP_443171.2

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
FCRL3	ENST00000368184.8	c.*402C>T		3_prime_UTR_variant	15/15	1	NM_052939.4	ENSP00000357167	P2

Frequencies

GnomAD3 genomes AF: 0.238 AC: 36217 AN: 151898 Hom.: 4471 Cov.: 32

Gnomad AFR AF: 0.195

Gnomad AMI AF: 0.274

Gnomad AMR AF: 0.252

Gnomad ASJ AF: 0.330

Gnomad EAS AF: 0.170

Gnomad SAS AF: 0.220

Gnomad FIN AF: 0.204

Gnomad MID AF: 0.392

Gnomad NFE AF: 0.267

Gnomad OTH AF: 0.281

GnomAD4 exome AF: 0.264 AC: 226771 AN: 858406 Hom.: 30281 Cov.: 32 AF XY: 0.264 AC XY: 105018 AN XY: 397654

Gnomad4 AFR exome AF: 0.188

Gnomad4 AMR exome AF: 0.218

Gnomad4 ASJ exome AF: 0.316

Gnomad4 EAS exome AF: 0.156

Gnomad4 SAS exome AF: 0.240

Gnomad4 FIN exome AF: 0.201

Gnomad4 NFE exome AF: 0.266

Gnomad4 OTH exome AF: 0.280

GnomAD4 genome AF: 0.238 AC: 36237 AN: 152018 Hom.: 4478 Cov.: 32 AF XY: 0.236 AC XY: 17503 AN XY: 74304

Gnomad4 AFR AF: 0.195

Gnomad4 AMR AF: 0.251

Gnomad4 ASJ AF: 0.330

Gnomad4 EAS AF: 0.170

Gnomad4 SAS AF: 0.221

Gnomad4 FIN AF: 0.204

Gnomad4 NFE AF: 0.267

Gnomad4 OTH AF: 0.283

Alfa AF: 0.268 Hom.: 7560

Bravo AF: 0.241

Asia WGS AF: 0.214 AC: 745 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.92
CADD	Benign	0.82
DANN	Benign	0.75

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: rs6691569; hg19: chr1-157648098;