rs2039401

Variant names:

• chr1-157578533-T-C
• rs2039401
• NM_031282.3:c.1370A>G

Variant summary

Our verdict is Benign. The variant received -20 ACMG points: 0P and 20B. BP4_Strong BP6_Very_Strong BA1

The NM_031282.3(FCRL4):​c.1370A>G​(p.Lys457Arg) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00291 in 1,613,810 control chromosomes in the GnomAD database, including 107 homozygotes. In-silico tool predicts a benign outcome for this variant. 15/21 in silico tools predict a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★★).

• Frequency:
  • Genomes: 𝑓 0.016 (39 hom., cov: 32)
  • Exomes 𝑓: 0.0016 (68 hom.)
• Consequence: FCRL4 NM_031282.3 missense
• Clinical Significance: Benign criteria provided, multiple submitters, no conflicts B:2
• Conservation: PhyloP100: -1.05
• Publications: 8 publications found

Genes affected

FCRL4 (HGNC:18507): (Fc receptor like 4) 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 has four extracellular C2-type immunoglobulin domains, a transmembrane domain and a cytoplasmic domain that contains three immune-receptor tyrosine-based inhibitory motifs. This protein may play a role in the function of memory B-cells in the epithelia. Aberrations in the chromosomal region encoding this gene are associated with non-Hodgkin lymphoma and multiple myeloma. [provided by RefSeq, Apr 2009]

ACMG classification

Our verdict: Benign. The variant received -20 ACMG points.

• BP4: Computational evidence support a benign effect (MetaRNN=0.0031429827).
• BP6: Variant 1-157578533-T-C is Benign according to our data. Variant chr1-157578533-T-C is described in ClinVar as Benign. ClinVar VariationId is 783950.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars.
• BA1: GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.0529 is higher than 0.05.

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_031282.3. 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
	FCRL4	NM_031282.3	MANE Select	c.1370A>G	p.Lys457Arg	missense	Exon 10 of 12	NP_112572.1	Q96PJ5-1

Ensembl Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	FCRL4	ENST00000271532.2	TSL:1 MANE Select	c.1370A>G	p.Lys457Arg	missense	Exon 10 of 12	ENSP00000271532.1	Q96PJ5-1
	FCRL4	ENST00000448509.6	TSL:2	n.1338A>G		non_coding_transcript_exon	Exon 7 of 9
	FCRL4	ENST00000479869.1	TSL:3	n.310A>G		non_coding_transcript_exon	Exon 3 of 5

Frequencies

GnomAD3 genomes AF: 0.0156 AC: 2369 AN: 152140 Hom.: 39 Cov.: 32

Gnomad AFR AF: 0.0549

Gnomad AMI AF: 0.00

Gnomad AMR AF: 0.00386

Gnomad ASJ AF: 0.00

Gnomad EAS AF: 0.00

Gnomad SAS AF: 0.000207

Gnomad FIN AF: 0.00

Gnomad MID AF: 0.00

Gnomad NFE AF: 0.000191

Gnomad OTH AF: 0.0115

GnomAD2 exomes AF: 0.00408 AC: 1025 AN: 251322 AF XY: 0.00301

Gnomad AFR exome AF: 0.0558

Gnomad AMR exome AF: 0.00278

Gnomad ASJ exome AF: 0.00

Gnomad EAS exome AF: 0.00

Gnomad FIN exome AF: 0.00

Gnomad NFE exome AF: 0.0000968

Gnomad OTH exome AF: 0.00131

GnomAD4 exome AF: 0.00159 AC: 2322 AN: 1461552 Hom.: 68 Cov.: 31 AF XY: 0.00132 AC XY: 962 AN XY: 727110

African (AFR) AF: 0.0567 AC: 1895 AN: 33438

American (AMR) AF: 0.00311 AC: 139 AN: 44724

Ashkenazi Jewish (ASJ) AF: 0.00 AC: 0 AN: 26132

East Asian (EAS) AF: 0.00 AC: 0 AN: 39696

South Asian (SAS) AF: 0.000104 AC: 9 AN: 86254

European-Finnish (FIN) AF: 0.0000374 AC: 2 AN: 53416

Middle Eastern (MID) AF: 0.00121 AC: 7 AN: 5768

European-Non Finnish (NFE) AF: 0.0000504 AC: 56 AN: 1111736

Other (OTH) AF: 0.00354 AC: 214 AN: 60388

GnomAD4 genome AF: 0.0156 AC: 2372 AN: 152258 Hom.: 39 Cov.: 32 AF XY: 0.0149 AC XY: 1112 AN XY: 74458

African (AFR) AF: 0.0548 AC: 2275 AN: 41528

American (AMR) AF: 0.00386 AC: 59 AN: 15290

Ashkenazi Jewish (ASJ) AF: 0.00 AC: 0 AN: 3472

East Asian (EAS) AF: 0.00 AC: 0 AN: 5186

South Asian (SAS) AF: 0.000207 AC: 1 AN: 4824

European-Finnish (FIN) AF: 0.00 AC: 0 AN: 10616

Middle Eastern (MID) AF: 0.00 AC: 0 AN: 294

European-Non Finnish (NFE) AF: 0.000191 AC: 13 AN: 68022

Other (OTH) AF: 0.0114 AC: 24 AN: 2114

Alfa AF: 0.00602 Hom.: 64

Bravo AF: 0.0176

ESP6500AA AF: 0.0470 AC: 207

ESP6500EA AF: 0.000233 AC: 2

ExAC AF: 0.00498 AC: 604

Asia WGS AF: 0.00289 AC: 10 AN: 3478

EpiCase AF: 0.000109

EpiControl AF: 0.0000593

ClinVar

ClinVar submissions

Significance: Benign

Revision: criteria provided, multiple submitters, no conflicts

Pathogenic	VUS	Benign	Condition
-	-	2	not provided (2)

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
AlphaMissense	Benign	0.069
BayesDel_addAF	Benign	-0.75	T
BayesDel_noAF	Benign	-0.81
CADD	Benign	0.33
DANN	Benign	0.73
DEOGEN2	Benign	0.0035	T
Eigen	Benign	-1.3
Eigen_PC	Benign	-1.4
FATHMM_MKL	Benign	0.0057	N
LIST_S2	Benign	0.35	T
MetaRNN	Benign	0.0031	T
MetaSVM	Benign	-0.94	T
MutationAssessor	Benign	0.52	N
PhyloP100		-1.1
PrimateAI	Benign	0.23	T
PROVEAN	Benign	-0.28	N
REVEL	Benign	0.0090
Sift	Benign	0.53	T
Sift4G	Benign	0.50	T
Polyphen		0.0030	B
Vest4		0.049
MVP		0.22
MPC		0.030
ClinPred		0.0059	T
GERP RS		-5.3
Varity_R		0.045
gMVP		0.046
Mutation Taster		=100/0	polymorphism

Splicing

Name	Calibrated prediction	Score	Prediction
SpliceAI score (max)		0.030		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: rs2039401; hg19: chr1-157548323; COSMIC: COSV99070279;