chr1-157515721-G-T

Variant names:

• chr1-157515721-G-T
• rs140845798
• NM_031281.3:c.2888C>A

Variant summary

Our verdict is Uncertain significance. Variant got 0 ACMG points: 2P and 2B. PM2 BP4_Moderate

The NM_031281.3(FCRL5):​c.2888C>A​(p.Pro963Gln) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant was absent in control chromosomes in GnomAD project. In-silico tool predicts a benign outcome for this variant. 13/19 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. P963L) has been classified as Uncertain significance.

• Frequency: Genomes: not found (cov: 33)
• Consequence: FCRL5 NM_031281.3 missense
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.255

Genes affected

FCRL5 (HGNC:18508): (Fc receptor like 5) This gene encodes a member of the immunoglobulin receptor superfamily and the Fc-receptor like family. This gene and several other Fc receptor-like gene members are clustered on the long arm of chromosome 1. The encoded protein is a single-pass type I membrane protein and contains 8 immunoglobulin-like C2-type domains. This gene is implicated in B cell development and lymphomagenesis. Alternatively spliced transcript variants encoding different isoforms have been identified. [provided by RefSeq, Sep 2010]

ACMG classification

Verdict is Uncertain_significance. Variant got 0 ACMG points.

• PM2: Very rare variant in population databases, with high coverage
• BP4: Computational evidence support a benign effect (MetaRNN=0.179705).

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
FCRL5	NM_031281.3	c.2888C>A	p.Pro963Gln	missense_variant	Exon 17 of 17	ENST00000361835.8	NP_112571.2

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
FCRL5	ENST00000361835.8	c.2888C>A	p.Pro963Gln	missense_variant	Exon 17 of 17	1	NM_031281.3	ENSP00000354691.3
FCRL5	ENST00000461387.5	n.2165C>A		non_coding_transcript_exon_variant	Exon 7 of 7	2
FCRL5	ENST00000462218.1	n.276C>A		non_coding_transcript_exon_variant	Exon 2 of 2	2
FCRL5	ENST00000497286.5	n.1981C>A		non_coding_transcript_exon_variant	Exon 9 of 9	2

Frequencies

GnomAD3 genomes Cov.: 33

GnomAD4 exome Cov.: 31

GnomAD4 genome Cov.: 33

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
AlphaMissense	Benign	0.11
BayesDel_addAF	Benign	-0.12	T
BayesDel_noAF	Benign	-0.41
CADD	Benign	13
DANN	Benign	0.86
DEOGEN2	Benign	0.0042	T
Eigen	Benign	-0.46
Eigen_PC	Benign	-0.64
FATHMM_MKL	Benign	0.036	N
LIST_S2	Benign	0.48	T
M_CAP	Benign	0.044	D
MetaRNN	Benign	0.18	T
MetaSVM	Benign	-1.1	T
PROVEAN	Benign	-1.1	N
REVEL	Benign	0.060
Sift	Uncertain	0.017	D
Sift4G	Benign	0.078	T
Polyphen		0.97	D
Vest4		0.062
MutPred		0.38		Loss of loop (P = 0.0128);
MVP		0.40
MPC		0.33
ClinPred		0.34	T
GERP RS		1.9
Varity_R		0.038
gMVP		0.13

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

Publications

LitVar

Other links and lift over

dbSNP: rs140845798; hg19: chr1-157485511; COSMIC: COSV100709030; COSMIC: COSV100709030;