NM_052939.4:c.*974T>A

Variant names:

• chr1-157677736-A-T
• rs11264793
• NM_052939.4:c.*974T>A

Variant summary

Our verdict is Benign. The variant received -12 ACMG points: 0P and 12B. BP4_Strong BA1

The NM_052939.4(FCRL3):​c.*974T>A variant causes a 3 prime UTR change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.265 in 597,478 control chromosomes in the GnomAD database, including 21,829 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 (6683 hom., cov: 32)
  • Exomes 𝑓: 0.26 (15146 hom.)
• Consequence: FCRL3 NM_052939.4 3_prime_UTR
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.192
• Publications: 8 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=-0.93).
• BA1: GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.412 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

Selected	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	FCRL3	NM_052939.4	MANE Select	c.*974T>A		3_prime_UTR	Exon 15 of 15	NP_443171.2
	FCRL3	NM_001320333.2		c.2173-968T>A		intron	N/A	NP_001307262.1
	FCRL3	NR_135214.2		n.2542+859T>A		intron	N/A

Ensembl Transcripts

Selected	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	FCRL3	ENST00000368184.8	TSL:1 MANE Select	c.*974T>A		3_prime_UTR	Exon 15 of 15	ENSP00000357167.3
	FCRL3	ENST00000368186.9	TSL:1	c.2173-968T>A		intron	N/A	ENSP00000357169.5
	FCRL3	ENST00000477837.5	TSL:1	n.*115+859T>A		intron	N/A	ENSP00000433430.1

Frequencies

GnomAD3 genomes AF: 0.282 AC: 42845 AN: 151990 Hom.: 6670 Cov.: 32

Gnomad AFR AF: 0.417

Gnomad AMI AF: 0.276

Gnomad AMR AF: 0.223

Gnomad ASJ AF: 0.244

Gnomad EAS AF: 0.236

Gnomad SAS AF: 0.173

Gnomad FIN AF: 0.219

Gnomad MID AF: 0.203

Gnomad NFE AF: 0.237

Gnomad OTH AF: 0.262

GnomAD4 exome AF: 0.259 AC: 115401 AN: 445372 Hom.: 15146 Cov.: 6 AF XY: 0.259 AC XY: 54333 AN XY: 209598

African (AFR) AF: 0.435 AC: 3433 AN: 7894

American (AMR) AF: 0.205 AC: 108 AN: 526

Ashkenazi Jewish (ASJ) AF: 0.246 AC: 675 AN: 2748

East Asian (EAS) AF: 0.245 AC: 450 AN: 1838

South Asian (SAS) AF: 0.183 AC: 1600 AN: 8754

European-Finnish (FIN) AF: 0.232 AC: 33 AN: 142

Middle Eastern (MID) AF: 0.209 AC: 182 AN: 870

European-Non Finnish (NFE) AF: 0.258 AC: 105349 AN: 408060

Other (OTH) AF: 0.246 AC: 3571 AN: 14540

GnomAD4 genome AF: 0.282 AC: 42881 AN: 152106 Hom.: 6683 Cov.: 32 AF XY: 0.277 AC XY: 20586 AN XY: 74348

African (AFR) AF: 0.417 AC: 17297 AN: 41470

American (AMR) AF: 0.223 AC: 3404 AN: 15292

Ashkenazi Jewish (ASJ) AF: 0.244 AC: 846 AN: 3468

East Asian (EAS) AF: 0.236 AC: 1223 AN: 5178

South Asian (SAS) AF: 0.171 AC: 825 AN: 4822

European-Finnish (FIN) AF: 0.219 AC: 2320 AN: 10578

Middle Eastern (MID) AF: 0.211 AC: 62 AN: 294

European-Non Finnish (NFE) AF: 0.237 AC: 16105 AN: 67984

Other (OTH) AF: 0.260 AC: 548 AN: 2110

Alfa AF: 0.252 Hom.: 714

Bravo AF: 0.291

Asia WGS AF: 0.183 AC: 635 AN: 3476

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.93
CADD	Benign	0.91
DANN	Benign	0.42
PhyloP100		-0.19
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: rs11264793; hg19: chr1-157647526;