Variant 1-157802110-C-T details in Genebe, Genetics Data Aggregator

Variant summary

Our verdict is Uncertain significance. Variant got 1 ACMG points: 2P and 1B. PM2BP4

The NM_052938.5(FCRL1):c.691G>A(p.Ala231Thr) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00000274 in 1,461,868 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a benign outcome for this variant. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar.

Frequency

Genomes: not found (cov: 32)

Exomes 𝑓: 0.0000027 ( 0 hom. )

Consequence

FCRL1
NM_052938.5 missense

Scores

Clinical Significance

Uncertain significance criteria provided, single submitter U:1

Conservation

PhyloP100: 1.14

Variant links:

Genes affected

FCRL1 (HGNC:18509): (Fc receptor like 1) 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 contains three extracellular C2-like immunoglobulin domains, a transmembrane domain and a cytoplasmic domain with two immunoreceptor-tyrosine activation motifs. This protein may play a role in the regulation of cancer cell growth. Alternative splicing results in multiple transcript variants. [provided by RefSeq, Apr 2009]

FCRL1 links:

FCRL1 (HGNC:):

FCRL1 links:

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ACMG classification

Classification made for transcript

Verdict is Uncertain_significance. Variant got 1 ACMG points.

PM2

Very rare variant in population databases, with high coverage;

BP4

Computational evidence support a benign effect (MetaRNN=0.3305451).

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
FCRL1	NM_052938.5 linkuse as main transcript	c.691G>A	p.Ala231Thr	missense_variant	5/11	ENST00000368176.8	NP_443170.1	Q96LA6-1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
FCRL1	ENST00000368176.8 linkuse as main transcript	c.691G>A	p.Ala231Thr	missense_variant	5/11	1	NM_052938.5	ENSP00000357158.3		Q96LA6-1

Frequencies

GnomAD3 genomes

Cov.:

GnomAD4 exome

AF:

0.00000274

AC:

AN:

1461868

Hom.:

Cov.:

AF XY:

0.00000138

AC XY:

AN XY:

727236

show subpopulations

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:

0.00000360

Gnomad4 OTH exome

AF:

0.00

GnomAD4 genome

Cov.:

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

Oct 12, 2024

The c.691G>A (p.A231T) alteration is located in exon 5 (coding exon 5) of the FCRL1 gene. This alteration results from a G to A substitution at nucleotide position 691, causing the alanine (A) at amino acid position 231 to be replaced by a threonine (T). 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

0.16

BayesDel_addAF

Benign

-0.15

BayesDel_noAF

Benign

-0.46

CADD

Benign

DANN

Uncertain

1.0

DEOGEN2

Benign

0.020

.;T;.

Eigen

Uncertain

0.28

Eigen_PC

Benign

0.13

FATHMM_MKL

Benign

0.24

LIST_S2

Benign

0.26

T;T;T

M_CAP

Benign

0.0042

MetaRNN

Benign

0.33

T;T;T

MetaSVM

Benign

-1.1

MutationAssessor

Uncertain

2.5

M;M;M

PrimateAI

Benign

0.34

PROVEAN

Uncertain

-3.0

D;D;D

REVEL

Benign

0.14

Sift

Uncertain

0.012

D;D;D

Sift4G

Benign

0.13

T;D;D

Polyphen

0.85

P;D;D

Vest4

0.33

MutPred

0.54

Gain of catalytic residue at A231 (P = 0.0022);Gain of catalytic residue at A231 (P = 0.0022);Gain of catalytic residue at A231 (P = 0.0022);

MVP

0.47

MPC

0.39

ClinPred

0.91

GERP RS

4.9

Varity_R

0.27

gMVP

0.35

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

Publications

No publications associated with this variant yet.

Variant summary

Frequency

Consequence

Scores

Clinical Significance

Conservation

ACMG classification

Transcripts

RefSeq

Ensembl

Frequencies

ClinVar

Submissions by phenotype

Computational scores

Splicing

Publications

Other links and lift over