1-157700500-C-G

Variant names:

• chr1-157700500-C-G
• rs945635
• ENST00000477837.5:n.-11G>C

Variant summary

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

The ENST00000477837.5(FCRL3):​n.-11G>C variant causes a non coding transcript exon change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.461 in 1,613,508 control chromosomes in the GnomAD database, including 179,518 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 0.55 (25937 hom., cov: 32)
  • Exomes 𝑓: 0.45 (153581 hom.)
• Consequence: FCRL3 ENST00000477837.5 non_coding_transcript_exon
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.237
• Publications: 53 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=-0.9).
• BA1: GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.846 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
FCRL3	NM_052939.4	c.-11G>C		5_prime_UTR_variant	Exon 2 of 15	ENST00000368184.8	NP_443171.2

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
FCRL3	ENST00000368184.8	c.-11G>C		5_prime_UTR_variant	Exon 2 of 15	1	NM_052939.4	ENSP00000357167.3

Frequencies

GnomAD3 genomes AF: 0.553 AC: 83943 AN: 151908 Hom.: 25893 Cov.: 32

Gnomad AFR AF: 0.853

Gnomad AMI AF: 0.458

Gnomad AMR AF: 0.484

Gnomad ASJ AF: 0.464

Gnomad EAS AF: 0.412

Gnomad SAS AF: 0.307

Gnomad FIN AF: 0.418

Gnomad MID AF: 0.513

Gnomad NFE AF: 0.441

Gnomad OTH AF: 0.526

GnomAD2 exomes AF: 0.449 AC: 112552 AN: 250434 AF XY: 0.434

Gnomad AFR exome AF: 0.868

Gnomad AMR exome AF: 0.457

Gnomad ASJ exome AF: 0.451

Gnomad EAS exome AF: 0.403

Gnomad FIN exome AF: 0.408

Gnomad NFE exome AF: 0.440

Gnomad OTH exome AF: 0.444

GnomAD4 exome AF: 0.452 AC: 660444 AN: 1461482 Hom.: 153581 Cov.: 53 AF XY: 0.445 AC XY: 323753 AN XY: 727024

African (AFR) AF: 0.872 AC: 29181 AN: 33460

American (AMR) AF: 0.455 AC: 20302 AN: 44666

Ashkenazi Jewish (ASJ) AF: 0.448 AC: 11711 AN: 26132

East Asian (EAS) AF: 0.404 AC: 16019 AN: 39680

South Asian (SAS) AF: 0.313 AC: 26972 AN: 86242

European-Finnish (FIN) AF: 0.415 AC: 22125 AN: 53376

Middle Eastern (MID) AF: 0.481 AC: 2775 AN: 5768

European-Non Finnish (NFE) AF: 0.452 AC: 502865 AN: 1111786

Other (OTH) AF: 0.472 AC: 28494 AN: 60372

GnomAD4 genome AF: 0.553 AC: 84034 AN: 152026 Hom.: 25937 Cov.: 32 AF XY: 0.545 AC XY: 40494 AN XY: 74286

African (AFR) AF: 0.853 AC: 35398 AN: 41490

American (AMR) AF: 0.483 AC: 7376 AN: 15272

Ashkenazi Jewish (ASJ) AF: 0.464 AC: 1610 AN: 3470

East Asian (EAS) AF: 0.412 AC: 2129 AN: 5168

South Asian (SAS) AF: 0.307 AC: 1478 AN: 4816

European-Finnish (FIN) AF: 0.418 AC: 4418 AN: 10558

Middle Eastern (MID) AF: 0.524 AC: 154 AN: 294

European-Non Finnish (NFE) AF: 0.441 AC: 29943 AN: 67944

Other (OTH) AF: 0.528 AC: 1111 AN: 2104

Alfa AF: 0.369 Hom.: 1691

Bravo AF: 0.575

Asia WGS AF: 0.433 AC: 1505 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.90
CADD	Benign	1.9
DANN	Benign	0.46
PhyloP100		-0.24
PromoterAI		0.0097	Neutral
Mutation Taster		=300/0	polymorphism (auto)

Splicing

Name	Calibrated prediction	Score	Prediction
SpliceAI score (max)		0.040		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: rs945635; hg19: chr1-157670290; COSMIC: COSV63841306; COSMIC: COSV63841306;