Genetic Variant NM_031281.3:c.2557G>T (chr1-157520506-C-A) – ACMG Classification: Uncertain_significance (0 pts)

Variant summary

Our verdict is Uncertain significance. The variant received 0 ACMG points: 2P and 2B. PM2BP4_Moderate

The NM_031281.3(FCRL5):c.2557G>T(p.Ala853Ser) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.000000702 in 1,423,902 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. A853T) has been classified as Likely benign.

Frequency

Genomes: not found (cov: 33)

Exomes 𝑓: 7.0e-7 ( 0 hom. )

Consequence

FCRL5
NM_031281.3 missense

Scores

Clinical Significance

Not reported in ClinVar

Conservation

PhyloP100: -0.0580

Publications

0 publications found

Variant links:

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]

FCRL5 links:

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ACMG classification

Classification was made for transcript

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=0.14858213).

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_031281.3. 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
	FCRL5	NM_031281.3	MANE Select	c.2557G>T	p.Ala853Ser	missense	Exon 12 of 17	NP_112571.2	Q96RD9-1
	FCRL5	NM_001195388.2		c.2557G>T	p.Ala853Ser	missense	Exon 12 of 17	NP_001182317.1

Ensembl Transcripts

Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
FCRL5	ENST00000361835.8	TSL:1 MANE Select	c.2557G>T	p.Ala853Ser	missense	Exon 12 of 17	ENSP00000354691.3	Q96RD9-1
FCRL5	ENST00000908742.1		c.2515+511G>T		intron	N/A	ENSP00000578801.1
FCRL5	ENST00000461387.5	TSL:2	n.1834G>T		non_coding_transcript_exon	Exon 2 of 7

Frequencies

GnomAD3 genomes

Cov.:

GnomAD4 exome

AF:

7.02e-7

AC:

AN:

1423902

Hom.:

Cov.:

AF XY:

0.00

AC XY:

AN XY:

704734

show subpopulations

African (AFR)

AF:

0.00

AC:

AN:

32484

American (AMR)

AF:

0.00

AC:

AN:

39560

Ashkenazi Jewish (ASJ)

AF:

0.00

AC:

AN:

25450

East Asian (EAS)

AF:

0.00

AC:

AN:

37318

South Asian (SAS)

AF:

0.00

AC:

AN:

80930

European-Finnish (FIN)

AF:

0.00

AC:

AN:

50796

Middle Eastern (MID)

AF:

0.00

AC:

AN:

5708

European-Non Finnish (NFE)

AF:

9.15e-7

AC:

AN:

1092678

Other (OTH)

AF:

0.00

AC:

AN:

58978

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.475

Heterozygous variant carriers

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Exome Het

Variant carriers

<30

30-35

35-40

40-45

45-50

50-55

55-60

60-65

65-70

70-75

75-80

>80

Age

GnomAD4 genome

Cov.:

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name

Calibrated prediction

Score

Prediction

AlphaMissense

Benign

0.10

BayesDel_addAF

Benign

-0.32

BayesDel_noAF

Benign

-0.70

CADD

Benign

9.1

(source)

DANN

Benign

0.76

DEOGEN2

Benign

0.00079

Eigen

Benign

-1.1

Eigen_PC

Benign

-1.0

FATHMM_MKL

Benign

0.19

LIST_S2

Benign

0.17

M_CAP

Benign

0.0034

MetaRNN

Benign

0.15

MetaSVM

Benign

-0.95

MutationAssessor

Benign

1.2

PhyloP100

-0.058

PrimateAI

Benign

0.34

PROVEAN

Benign

-0.050

REVEL

Benign

0.023

Sift

Benign

0.047

Sift4G

Uncertain

0.037

Polyphen

0.026

Vest4

0.075

MutPred

0.44

Gain of sheet (P = 0.0125)

MVP

0.17

MPC

0.065

ClinPred

0.082

GERP RS

2.5

Varity_R

0.035

gMVP

0.21

Mutation Taster

=96/4

polymorphism

(source)

Splicing

Name

Calibrated prediction

Score

Prediction

SpliceAI score (max)

0.060

Details are displayed if max score is > 0.2

Find out detailed SpliceAI scores and Pangolin per-transcript scores at spliceailookup.broadinstitute.org

Publications

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Variant summary

Frequency

Consequence

Scores

Clinical Significance

Conservation

Publications

ACMG classification

Variant Effect in Transcripts

RefSeq Transcripts

Ensembl Transcripts

Frequencies

Age Distribution

ClinVar

Computational scores

Splicing

Publications

Other links and lift over