rs6691569

Variant names:

• chr1-157678308-G-A
• rs6691569
• NM_052939.4:c.*402C>T

Variant summary

Our verdict is Benign. The variant received -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
• Publications: 14 publications found

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

Our verdict: Benign. The variant received -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.

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_052939.4. You can select a different transcript below to see updated ACMG assignments.

RefSeq Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	FCRL3	NM_052939.4	MANE Select	c.*402C>T		3_prime_UTR	Exon 15 of 15	NP_443171.2
	FCRL3	NM_001320333.2		c.2172+435C>T		intron	N/A	NP_001307262.1
	FCRL3	NR_135214.2		n.2542+287C>T		intron	N/A

Ensembl Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	FCRL3	ENST00000368184.8	TSL:1 MANE Select	c.*402C>T		3_prime_UTR	Exon 15 of 15	ENSP00000357167.3
	FCRL3	ENST00000368186.9	TSL:1	c.2172+435C>T		intron	N/A	ENSP00000357169.5
	FCRL3	ENST00000477837.5	TSL:1	n.*115+287C>T		intron	N/A	ENSP00000433430.1

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

African (AFR) AF: 0.188 AC: 3118 AN: 16576

American (AMR) AF: 0.218 AC: 804 AN: 3684

Ashkenazi Jewish (ASJ) AF: 0.316 AC: 1806 AN: 5718

East Asian (EAS) AF: 0.156 AC: 828 AN: 5324

South Asian (SAS) AF: 0.240 AC: 4443 AN: 18532

European-Finnish (FIN) AF: 0.201 AC: 204 AN: 1016

Middle Eastern (MID) AF: 0.335 AC: 572 AN: 1710

European-Non Finnish (NFE) AF: 0.266 AC: 206979 AN: 777164

Other (OTH) AF: 0.280 AC: 8017 AN: 28682

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

African (AFR) AF: 0.195 AC: 8072 AN: 41480

American (AMR) AF: 0.251 AC: 3840 AN: 15286

Ashkenazi Jewish (ASJ) AF: 0.330 AC: 1143 AN: 3464

East Asian (EAS) AF: 0.170 AC: 877 AN: 5150

South Asian (SAS) AF: 0.221 AC: 1065 AN: 4816

European-Finnish (FIN) AF: 0.204 AC: 2158 AN: 10560

Middle Eastern (MID) AF: 0.387 AC: 113 AN: 292

European-Non Finnish (NFE) AF: 0.267 AC: 18124 AN: 67954

Other (OTH) AF: 0.283 AC: 596 AN: 2106

Alfa AF: 0.264 Hom.: 9352

Bravo AF: 0.241

Asia WGS AF: 0.214 AC: 745 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.92
CADD	Benign	0.82
DANN	Benign	0.75
PhyloP100		-0.80
Mutation Taster		=100/0	polymorphism (auto)

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

Other links and lift over

dbSNP: rs6691569; hg19: chr1-157648098;