rs10489678

chr1-157699878-G-Achr1-157699878-G-Cchr1-157699878-G-T

Variant summary

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

The NM_052939.4(FCRL3):c.32-166C>T variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.197 in 151,974 control chromosomes in the GnomAD database, including 3,076 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 0.20 (3076 hom., cov: 32)
• Consequence: FCRL3 NM_052939.4 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.537

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=-0.93).
• BA1: GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.241 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
FCRL3	NM_052939.4	c.32-166C>T		intron_variant		ENST00000368184.8

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
FCRL3	ENST00000368184.8	c.32-166C>T		intron_variant		1	NM_052939.4	P2

Frequencies

GnomAD3 genomes AF: 0.197 AC: 29918 AN: 151856 Hom.: 3071 Cov.: 32

Gnomad AFR AF: 0.244

Gnomad AMI AF: 0.188

Gnomad AMR AF: 0.186

Gnomad ASJ AF: 0.203

Gnomad EAS AF: 0.180

Gnomad SAS AF: 0.122

Gnomad FIN AF: 0.182

Gnomad MID AF: 0.140

Gnomad NFE AF: 0.180

Gnomad OTH AF: 0.185

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

GnomAD4 genome AF: 0.197 AC: 29946 AN: 151974 Hom.: 3076 Cov.: 32 AF XY: 0.195 AC XY: 14510 AN XY: 74250

Gnomad4 AFR AF: 0.244

Gnomad4 AMR AF: 0.186

Gnomad4 ASJ AF: 0.203

Gnomad4 EAS AF: 0.180

Gnomad4 SAS AF: 0.121

Gnomad4 FIN AF: 0.182

Gnomad4 NFE AF: 0.180

Gnomad4 OTH AF: 0.183

Alfa AF: 0.110 Hom.: 203

Bravo AF: 0.202

Asia WGS AF: 0.146 AC: 507 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.93
Cadd	Benign	0.48
Dann	Benign	0.79

Splicing

Name	Calibrated prediction	Score	Prediction
SpliceAI score (max)		0.010		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: rs10489678; hg19: chr1-157669668; COSMIC: COSV63841118; COSMIC: COSV63841118;