Variant 1-157580330-T-C details in Genebe, Genetics Data Aggregator

Variant summary

Our verdict is Uncertain significance. Variant got 0 ACMG points: 2P and 2B. PM2BP4_Moderate

The NM_031282.3(FCRL4):c.1268A>G(p.Asp423Gly) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00000657 in 152,164 control chromosomes in the GnomAD database, with no homozygous occurrence. 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 Uncertain significance (★). Another variant affecting the same amino acid position, but resulting in a different missense (i.e. D423E) has been classified as Uncertain significance.

Frequency

Genomes: 𝑓 0.0000066 ( 0 hom., cov: 33)

Consequence

FCRL4
NM_031282.3 missense

Scores

Clinical Significance

Uncertain significance criteria provided, single submitter U:1

Conservation

PhyloP100: 0.253

Variant links:

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 links:

FCRL4 (HGNC:):

FCRL4 links:

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ACMG classification

Classification made for transcript

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=0.08780137).

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
FCRL4	NM_031282.3 linkuse as main transcript	c.1268A>G	p.Asp423Gly	missense_variant	8/12	ENST00000271532.2	NP_112572.1	Q96PJ5-1
FCRL4	XM_011510034.2 linkuse as main transcript	c.1265A>G	p.Asp422Gly	missense_variant	8/12		XP_011508336.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	UniProt
FCRL4	ENST00000271532.2 linkuse as main transcript	c.1268A>G	p.Asp423Gly	missense_variant	8/12	1	NM_031282.3	ENSP00000271532.1	Q96PJ5-1
FCRL4	ENST00000448509.6 linkuse as main transcript	n.1009A>G		non_coding_transcript_exon_variant	6/9	2
FCRL4	ENST00000479869.1 linkuse as main transcript	n.208A>G		non_coding_transcript_exon_variant	1/5	3

Frequencies

GnomAD3 genomes

AF:

0.00000657

AC:

AN:

152164

Hom.:

Cov.:

show subpopulations

Gnomad AFR

AF:

0.00

Gnomad AMI

AF:

0.00

Gnomad AMR

AF:

0.00

Gnomad ASJ

AF:

0.00

Gnomad EAS

AF:

0.00

Gnomad SAS

AF:

0.00

Gnomad FIN

AF:

0.00

Gnomad MID

AF:

0.00

Gnomad NFE

AF:

0.0000147

Gnomad OTH

AF:

0.00

GnomAD4 exome

Cov.:

GnomAD4 genome

AF:

0.00000657

AC:

AN:

152164

Hom.:

Cov.:

AF XY:

0.00

AC XY:

AN XY:

74328

show subpopulations

Gnomad4 AFR

AF:

0.00

Gnomad4 AMR

AF:

0.00

Gnomad4 ASJ

AF:

0.00

Gnomad4 EAS

AF:

0.00

Gnomad4 SAS

AF:

0.00

Gnomad4 FIN

AF:

0.00

Gnomad4 NFE

AF:

0.0000147

Gnomad4 OTH

AF:

0.00

Bravo

AF:

0.00000378

ClinVar

Significance: Uncertain significance

Submissions summary: Uncertain:1

Revision: criteria provided, single submitter

LINK: link

Submissions by phenotype

not specified

Uncertain:1

Uncertain significance, criteria provided, single submitter

clinical testing

Ambry Genetics

Aug 16, 2021

The c.1268A>G (p.D423G) alteration is located in exon 8 (coding exon 8) of the FCRL4 gene. This alteration results from a A to G substitution at nucleotide position 1268, causing the aspartic acid (D) at amino acid position 423 to be replaced by a glycine (G). Based on insufficient or conflicting evidence, the clinical significance of this alteration remains unclear. -

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

AlphaMissense

Benign

0.068

BayesDel_addAF

Benign

-0.30

BayesDel_noAF

Benign

-0.67

CADD

Benign

DANN

Benign

0.90

DEOGEN2

Benign

0.018

Eigen

Benign

-0.62

Eigen_PC

Benign

-0.70

FATHMM_MKL

Benign

0.043

LIST_S2

Benign

0.49

M_CAP

Benign

0.0020

MetaRNN

Benign

0.088

MetaSVM

Benign

-1.0

MutationAssessor

Benign

1.7

PrimateAI

Benign

0.29

PROVEAN

Benign

-1.8

REVEL

Benign

0.018

Sift

Benign

0.17

Sift4G

Benign

0.13

Polyphen

0.44

Vest4

0.15

MutPred

0.34

Gain of MoRF binding (P = 0.0537);

MVP

0.31

MPC

0.039

ClinPred

0.18

GERP RS

2.7

Varity_R

0.059

gMVP

0.14

Splicing

Name

Calibrated prediction

Score

Prediction

SpliceAI score (max)

0.020

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

Below is the list of publications found by LitVar. It may be empty.

Variant summary

Frequency

Consequence

Scores

Clinical Significance

Conservation

ACMG classification

Transcripts

RefSeq

Ensembl

Frequencies

ClinVar

Submissions by phenotype

Computational scores

Splicing

Publications

LitVar

Other links and lift over