1-157578533-T-C

Position:

• chr1-157578533-T-C

Variant summary

Our verdict is Benign. Variant got -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. 14/20 in silico tools predict a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★★). Another nucleotide change resulting in same amino acid change has been previously reported as Likely benignin UniProt.

• 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

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]

FCRL4 (HGNC:):

ACMG classification

Verdict is Benign. Variant got -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 id 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.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
FCRL4	NM_031282.3	c.1370A>G	p.Lys457Arg	missense_variant	10/12	ENST00000271532.2	NP_112572.1
FCRL4	XM_011510034.2	c.1367A>G	p.Lys456Arg	missense_variant	10/12		XP_011508336.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
FCRL4	ENST00000271532.2	c.1370A>G	p.Lys457Arg	missense_variant	10/12	1	NM_031282.3	ENSP00000271532.1
FCRL4	ENST00000448509.6	n.1338A>G		non_coding_transcript_exon_variant	7/9	2
FCRL4	ENST00000479869.1	n.310A>G		non_coding_transcript_exon_variant	3/5	3

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

GnomAD3 exomes AF: 0.00408 AC: 1025 AN: 251322 Hom.: 25 AF XY: 0.00301 AC XY: 409 AN XY: 135836

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 SAS exome AF: 0.0000980

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

Gnomad4 AFR exome AF: 0.0567

Gnomad4 AMR exome AF: 0.00311

Gnomad4 ASJ exome AF: 0.00

Gnomad4 EAS exome AF: 0.00

Gnomad4 SAS exome AF: 0.000104

Gnomad4 FIN exome AF: 0.0000374

Gnomad4 NFE exome AF: 0.0000504

Gnomad4 OTH exome AF: 0.00354

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

Gnomad4 AFR AF: 0.0548

Gnomad4 AMR AF: 0.00386

Gnomad4 ASJ AF: 0.00

Gnomad4 EAS AF: 0.00

Gnomad4 SAS AF: 0.000207

Gnomad4 FIN AF: 0.00

Gnomad4 NFE AF: 0.000191

Gnomad4 OTH AF: 0.0114

Alfa AF: 0.00285 Hom.: 24

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

Significance: Benign

Submissions summary: Benign:2

Revision: criteria provided, multiple submitters, no conflicts

Submissions by phenotype

not provided Benign:2

Benign, criteria provided, single submitter	not provided	Breakthrough Genomics, Breakthrough Genomics	-	- -
Benign, criteria provided, single submitter	clinical testing	Labcorp Genetics (formerly Invitae), Labcorp	Apr 04, 2018	- -

Computational scores

Source: dbNSFP v4.3

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
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

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

Publications

LitVar

Other links and lift over

dbSNP: rs2039401; hg19: chr1-157548323; COSMIC: COSV99070279;