1-157575528-C-A

Variant names:

• chr1-157575528-C-A
• rs771971609
• NM_031282.3:c.1544G>T

Variant summary

Our verdict is Uncertain significance. The variant received 0 ACMG points: 2P and 2B. PM2 BP4_Moderate

The NM_031282.3(FCRL4):​c.1544G>T​(p.Ser515Ile) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.000000685 in 1,460,442 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a benign outcome for this variant. 16/22 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 variant affecting the same amino acid position, but resulting in a different missense (i.e. S515N) has been classified as Uncertain significance.

• Frequency:
  • Genomes: not found (cov: 32)
  • Exomes 𝑓: 6.8e-7 (0 hom.)
• Consequence: FCRL4 NM_031282.3 missense
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.143
• Publications: 0 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: Uncertain_significance. The variant received 0 ACMG points.

• PM2: Very rare variant in population databases, with high coverage
• BP4: Computational evidence support a benign effect (MetaRNN=0.095418036).

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.1544G>T	p.Ser515Ile	missense	Exon 12 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.1544G>T	p.Ser515Ile	missense	Exon 12 of 12	ENSP00000271532.1	Q96PJ5-1
	FCRL4	ENST00000448509.6	TSL:2	n.1512G>T		non_coding_transcript_exon	Exon 9 of 9
	FCRL4	ENST00000479869.1	TSL:3	n.*41G>T		downstream_gene	N/A

Frequencies

GnomAD3 genomes Cov.: 32

GnomAD4 exome AF: 6.85e-7 AC: 1 AN: 1460442 Hom.: 0 Cov.: 31 AF XY: 0.00 AC XY: 0 AN XY: 726574

African (AFR) AF: 0.00 AC: 0 AN: 33448

American (AMR) AF: 0.00 AC: 0 AN: 44674

Ashkenazi Jewish (ASJ) AF: 0.00 AC: 0 AN: 26116

East Asian (EAS) AF: 0.00 AC: 0 AN: 39676

South Asian (SAS) AF: 0.00 AC: 0 AN: 86182

European-Finnish (FIN) AF: 0.00 AC: 0 AN: 53378

Middle Eastern (MID) AF: 0.00 AC: 0 AN: 5596

European-Non Finnish (NFE) AF: 0.00 AC: 0 AN: 1111050

Other (OTH) AF: 0.0000166 AC: 1 AN: 60322

GnomAD4 genome Cov.: 32

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
AlphaMissense	Benign	0.075
BayesDel_addAF	Benign	-0.28	T
BayesDel_noAF	Benign	-0.64
CADD	Benign	12
DANN	Benign	0.94
DEOGEN2	Benign	0.0020	T
Eigen	Benign	-0.64
Eigen_PC	Benign	-0.88
FATHMM_MKL	Benign	0.023	N
LIST_S2	Benign	0.41	T
M_CAP	Benign	0.0029	T
MetaRNN	Benign	0.095	T
MetaSVM	Benign	-1.0	T
MutationAssessor	Benign	1.4	L
PhyloP100		-0.14
PrimateAI	Benign	0.30	T
PROVEAN	Benign	-0.58	N
REVEL	Benign	0.040
Sift	Uncertain	0.0050	D
Sift4G	Uncertain	0.010	D
Polyphen		0.98	D
Vest4		0.067
MutPred		0.19		Loss of phosphorylation at S515 (P = 0.0016)
MVP		0.29
MPC		0.041
ClinPred		0.12	T
GERP RS		-0.061
Varity_R		0.078
gMVP		0.23
Mutation Taster		=100/0	polymorphism

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

Other links and lift over

dbSNP: rs771971609; hg19: chr1-157545318;