chr1-157677736-A-T

Position:

• chr1-157677736-A-T

Variant summary

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

The ENST00000368184.8(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 ENST00000368184.8 3_prime_UTR
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.192

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 = 0.412 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
FCRL3	NM_052939.4	c.*974T>A		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.*974T>A		3_prime_UTR_variant	15/15	1	NM_052939.4	ENSP00000357167	P2

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

Gnomad4 AFR exome AF: 0.435

Gnomad4 AMR exome AF: 0.205

Gnomad4 ASJ exome AF: 0.246

Gnomad4 EAS exome AF: 0.245

Gnomad4 SAS exome AF: 0.183

Gnomad4 FIN exome AF: 0.232

Gnomad4 NFE exome AF: 0.258

Gnomad4 OTH exome AF: 0.246

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

Gnomad4 AFR AF: 0.417

Gnomad4 AMR AF: 0.223

Gnomad4 ASJ AF: 0.244

Gnomad4 EAS AF: 0.236

Gnomad4 SAS AF: 0.171

Gnomad4 FIN AF: 0.219

Gnomad4 NFE AF: 0.237

Gnomad4 OTH AF: 0.260

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 v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.93
CADD	Benign	0.91
DANN	Benign	0.42

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: rs11264793; hg19: chr1-157647526;