1-157692058-C-G

Position:

• chr1-157692058-C-G

Variant summary

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

The NM_052939.4(FCRL3):​c.1412-1525G>C variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.598 in 151,970 control chromosomes in the GnomAD database, including 29,599 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 0.60 (29597 hom., cov: 31)
  • Exomes 𝑓: 0.43 (2 hom.)
• Consequence: FCRL3 NM_052939.4 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.0340

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]

FCRL3 (HGNC:):

ACMG classification

Verdict is Benign. Variant got -12 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-1.02).
• BA1: GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.875 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
FCRL3	NM_052939.4	c.1412-1525G>C		intron_variant		ENST00000368184.8	NP_443171.2

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
FCRL3	ENST00000368184.8	c.1412-1525G>C		intron_variant		1	NM_052939.4	ENSP00000357167.3

Frequencies

GnomAD3 genomes AF: 0.597 AC: 90715 AN: 151838 Hom.: 29540 Cov.: 31

Gnomad AFR AF: 0.883

Gnomad AMI AF: 0.547

Gnomad AMR AF: 0.516

Gnomad ASJ AF: 0.519

Gnomad EAS AF: 0.413

Gnomad SAS AF: 0.380

Gnomad FIN AF: 0.458

Gnomad MID AF: 0.557

Gnomad NFE AF: 0.499

Gnomad OTH AF: 0.572

GnomAD4 exome AF: 0.429 AC: 6 AN: 14 Hom.: 2 Cov.: 0 AF XY: 0.400 AC XY: 4 AN XY: 10

Gnomad4 EAS exome AF: 0.500

Gnomad4 NFE exome AF: 0.500

Gnomad4 OTH exome AF: 0.00

GnomAD4 genome AF: 0.598 AC: 90820 AN: 151956 Hom.: 29597 Cov.: 31 AF XY: 0.589 AC XY: 43719 AN XY: 74244

Gnomad4 AFR AF: 0.883

Gnomad4 AMR AF: 0.516

Gnomad4 ASJ AF: 0.519

Gnomad4 EAS AF: 0.413

Gnomad4 SAS AF: 0.379

Gnomad4 FIN AF: 0.458

Gnomad4 NFE AF: 0.499

Gnomad4 OTH AF: 0.573

Alfa AF: 0.380 Hom.: 1020

Bravo AF: 0.618

Asia WGS AF: 0.464 AC: 1613 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-1.0
CADD	Benign	1.0
DANN	Benign	0.34

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: rs11264798; hg19: chr1-157661848;