chr1-157520539-C-T

Variant names:

• chr1-157520539-C-T
• rs771606459
• NM_031281.3:c.2524G>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.2524G>A​(p.Ala842Thr) 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. 15/21 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. A842S) has been classified as Uncertain significance.

• Frequency:
  • Genomes: not found (cov: 33)
  • Exomes 𝑓: 0.0 (0 hom.)
  • Failed GnomAD Quality Control
• Consequence: FCRL5 NM_031281.3 missense
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 0.685

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=0.08626875).

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
FCRL5	NM_031281.3	c.2524G>A	p.Ala842Thr	missense_variant	Exon 12 of 17	ENST00000361835.8	NP_112571.2

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
FCRL5	ENST00000361835.8	c.2524G>A	p.Ala842Thr	missense_variant	Exon 12 of 17	1	NM_031281.3	ENSP00000354691.3
FCRL5	ENST00000461387.5	n.1801G>A		non_coding_transcript_exon_variant	Exon 2 of 7	2
FCRL5	ENST00000497286.5	n.1617G>A		non_coding_transcript_exon_variant	Exon 4 of 9	2

Frequencies

GnomAD3 genomes Cov.: 33

GnomAD4 exome Data not reliable, filtered out with message: AC0 AF: 0.00 AC: 0 AN: 1431882 Hom.: 0 Cov.: 30 AF XY: 0.00 AC XY: 0 AN XY: 709412

Gnomad4 AFR exome AF: 0.00

Gnomad4 AMR exome AF: 0.00

Gnomad4 ASJ exome AF: 0.00

Gnomad4 EAS exome AF: 0.00

Gnomad4 SAS exome AF: 0.00

Gnomad4 FIN exome AF: 0.00

Gnomad4 NFE exome AF: 0.00

Gnomad4 OTH exome AF: 0.00

GnomAD4 genome Cov.: 33

Bravo AF: 0.00000378

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
AlphaMissense	Benign	0.075
BayesDel_addAF	Benign	-0.34	T
BayesDel_noAF	Benign	-0.73
CADD	Benign	16
DANN	Benign	0.97
DEOGEN2	Benign	0.00068	T
Eigen	Benign	-1.1
Eigen_PC	Benign	-1.1
FATHMM_MKL	Benign	0.014	N
LIST_S2	Benign	0.51	T
M_CAP	Benign	0.0054	T
MetaRNN	Benign	0.086	T
MetaSVM	Benign	-1.0	T
MutationAssessor	Benign	-0.34	N
PrimateAI	Benign	0.29	T
PROVEAN	Benign	-0.61	N
REVEL	Benign	0.021
Sift	Benign	0.038	D
Sift4G	Benign	0.47	T
Polyphen		0.73	P
Vest4		0.10
MutPred		0.36		Loss of methylation at R844 (P = 0.1086);
MVP		0.15
MPC		0.069
ClinPred		0.072	T
GERP RS		1.9
Varity_R		0.032
gMVP		0.14

Splicing

Name	Calibrated prediction	Score	Prediction
SpliceAI score (max)		0.070		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: rs771606459; hg19: chr1-157490329; COSMIC: COSV62518378; COSMIC: COSV62518378;