chr1-157698600-T-C

Variant names:

• chr1-157698600-T-C
• rs7522061
• NM_052939.4:c.82A>G

Variant summary

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

The NM_052939.4(FCRL3):​c.82A>G​(p.Asn28Asp) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.47 in 1,612,742 control chromosomes in the GnomAD database, including 180,413 homozygotes. In-silico tool predicts a benign outcome for this variant. 15/22 in silico tools predict a benign outcome for this variant. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar. Another nucleotide change resulting in the same amino acid substitution has been previously reported as Likely benign in UniProt.

• Frequency:
  • Genomes: 𝑓 0.50 (19728 hom., cov: 32)
  • Exomes 𝑓: 0.47 (160685 hom.)
• Consequence: FCRL3 NM_052939.4 missense
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.572

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 (MetaRNN=6.182872E-6).
• BA1: GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.622 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
FCRL3	NM_052939.4	c.82A>G	p.Asn28Asp	missense_variant	Exon 4 of 15	ENST00000368184.8	NP_443171.2

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
FCRL3	ENST00000368184.8	c.82A>G	p.Asn28Asp	missense_variant	Exon 4 of 15	1	NM_052939.4	ENSP00000357167.3

Frequencies

GnomAD3 genomes AF: 0.503 AC: 76408 AN: 151948 Hom.: 19697 Cov.: 32

Gnomad AFR AF: 0.628

Gnomad AMI AF: 0.526

Gnomad AMR AF: 0.474

Gnomad ASJ AF: 0.489

Gnomad EAS AF: 0.413

Gnomad SAS AF: 0.310

Gnomad FIN AF: 0.432

Gnomad MID AF: 0.513

Gnomad NFE AF: 0.465

Gnomad OTH AF: 0.497

GnomAD2 exomes AF: 0.448 AC: 112568 AN: 251050 AF XY: 0.438

Gnomad AFR exome AF: 0.633

Gnomad AMR exome AF: 0.457

Gnomad ASJ exome AF: 0.473

Gnomad EAS exome AF: 0.404

Gnomad FIN exome AF: 0.421

Gnomad NFE exome AF: 0.465

Gnomad OTH exome AF: 0.456

GnomAD4 exome AF: 0.466 AC: 680949 AN: 1460678 Hom.: 160685 Cov.: 41 AF XY: 0.460 AC XY: 334394 AN XY: 726734

Gnomad4 AFR exome AF: 0.633 AC: 21166 AN: 33464

Gnomad4 AMR exome AF: 0.453 AC: 20248 AN: 44708

Gnomad4 ASJ exome AF: 0.471 AC: 12308 AN: 26130

Gnomad4 EAS exome AF: 0.404 AC: 16027 AN: 39694

Gnomad4 SAS exome AF: 0.316 AC: 27291 AN: 86238

Gnomad4 FIN exome AF: 0.429 AC: 22906 AN: 53406

Gnomad4 NFE exome AF: 0.477 AC: 529539 AN: 1110916

Gnomad4 Remaining exome AF: 0.475 AC: 28650 AN: 60354

GnomAD4 genome AF: 0.503 AC: 76482 AN: 152064 Hom.: 19728 Cov.: 32 AF XY: 0.497 AC XY: 36945 AN XY: 74314

Gnomad4 AFR AF: 0.628 AC: 0.628489 AN: 0.628489

Gnomad4 AMR AF: 0.473 AC: 0.473498 AN: 0.473498

Gnomad4 ASJ AF: 0.489 AC: 0.488754 AN: 0.488754

Gnomad4 EAS AF: 0.412 AC: 0.412152 AN: 0.412152

Gnomad4 SAS AF: 0.309 AC: 0.309465 AN: 0.309465

Gnomad4 FIN AF: 0.432 AC: 0.431788 AN: 0.431788

Gnomad4 NFE AF: 0.465 AC: 0.465114 AN: 0.465114

Gnomad4 OTH AF: 0.499 AC: 0.499053 AN: 0.499053

Alfa AF: 0.477 Hom.: 82989

Bravo AF: 0.517

TwinsUK AF: 0.492 AC: 1824

ALSPAC AF: 0.475 AC: 1829

ESP6500AA AF: 0.628 AC: 2767

ESP6500EA AF: 0.465 AC: 3995

ExAC AF: 0.450 AC: 54625

Asia WGS AF: 0.421 AC: 1464 AN: 3478

EpiCase AF: 0.463

EpiControl AF: 0.469

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
AlphaMissense	Benign	0.079
BayesDel_addAF	Benign	-0.87	T
BayesDel_noAF	Benign	-0.88
CADD	Benign	0.0080
DANN	Benign	0.50
DEOGEN2	Benign	0.0064	.;T;.
Eigen	Benign	-2.1
Eigen_PC	Benign	-2.2
FATHMM_MKL	Benign	0.0045	N
LIST_S2	Benign	0.073	T;T;T
MetaRNN	Benign	0.0000062	T;T;T
MetaSVM	Benign	-0.98	T
MutationAssessor	Benign	-0.46	N;N;.
PrimateAI	Benign	0.24	T
PROVEAN	Benign	-0.95	N;N;.
REVEL	Benign	0.047
Sift	Benign	1.0	T;T;.
Sift4G	Benign	0.72	T;T;T
Polyphen		0.0	B;B;.
Vest4		0.021
MPC		0.0061
ClinPred		0.025	T
GERP RS		-11
Varity_R		0.043
gMVP		0.056
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

Publications

LitVar

Other links and lift over

dbSNP: rs7522061; hg19: chr1-157668390; COSMIC: COSV63840546; COSMIC: COSV63840546;