Genetic Variant FCMR:p.Arg301Lys (chr1-206909808-C-T) – ACMG Classification: Likely_benign (-2 pts)

Variant summary

Our verdict is Likely benign. The variant received -2 ACMG points: 2P and 4B. PM2BP4_Strong

The NM_005449.5(FCMR):c.902G>A(p.Arg301Lys) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00000351 in 1,425,958 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a benign outcome for this variant. 14/21 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. R301M) has been classified as Uncertain significance.

Frequency

Genomes: 𝑓 0.000013 ( 0 hom., cov: 32)

Exomes 𝑓: 0.0000024 ( 0 hom. )

Consequence

FCMR
NM_005449.5 missense

Scores

Clinical Significance

Not reported in ClinVar

Conservation

PhyloP100: -0.237

Publications

0 publications found

Variant links:

Genes affected

FCMR (HGNC:14315): (Fc mu receptor) Fc receptors specifically bind to the Fc region of immunoglobulins (Igs) to mediate the unique functions of each Ig class. FAIM3 encodes an Fc receptor for IgM (see MIM 147020) (Kubagawa et al., 2009 [PubMed 19858324]; Shima et al., 2010 [PubMed 20042454]).[supplied by OMIM, Jul 2010]

FCMR links:

Genome browser will be placed here

ACMG classification

Classification was made for transcript

Our verdict: Likely_benign. The variant received -2 ACMG points.

PM2

Very rare variant in population databases, with high coverage;

BP4

Computational evidence support a benign effect (MetaRNN=0.015093654).

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
FCMR	NM_005449.5 link	c.902G>A	p.Arg301Lys	missense_variant	Exon 6 of 8	ENST00000367091.8	NP_005440.1	O60667-1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
FCMR	ENST00000367091.8 link	c.902G>A	p.Arg301Lys	missense_variant	Exon 6 of 8	1	NM_005449.5	ENSP00000356058.3		O60667-1

Frequencies

GnomAD3 genomes

AF:

0.0000131

AC:

AN:

152216

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:

0.0000294

Gnomad OTH

AF:

0.00

GnomAD2 exomes

AF:

0.0000383

AC:

AN:

26094

AF XY:

0.00

show subpopulations

Gnomad AFR exome

AF:

0.00

Gnomad AMR exome

AF:

0.00

Gnomad ASJ exome

AF:

0.00

Gnomad EAS exome

AF:

0.00

Gnomad FIN exome

AF:

0.00

Gnomad NFE exome

AF:

0.0000933

Gnomad OTH exome

AF:

0.00

GnomAD4 exome

AF:

0.00000236

AC:

AN:

1273624

Hom.:

Cov.:

AF XY:

0.00000161

AC XY:

AN XY:

623050

show subpopulations

⚠️ The allele balance in gnomAD version 4 Exomes is significantly skewed from the expected value of 0.5.

African (AFR)

AF:

0.00

AC:

AN:

24606

American (AMR)

AF:

0.00

AC:

AN:

14634

Ashkenazi Jewish (ASJ)

AF:

0.00

AC:

AN:

19018

East Asian (EAS)

AF:

0.00

AC:

AN:

28224

South Asian (SAS)

AF:

0.00

AC:

AN:

60778

European-Finnish (FIN)

AF:

0.00

AC:

AN:

37664

Middle Eastern (MID)

AF:

0.00

AC:

AN:

4724

European-Non Finnish (NFE)

AF:

0.00000291

AC:

AN:

1031394

Other (OTH)

AF:

0.00

AC:

AN:

52582

⚠️ The allele balance in gnomAD4 Exomes is highly skewed from 0.5 (p-value = 0.066232), which strongly suggests a high chance of mosaicism in these individuals.

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.392

Heterozygous variant carriers

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

GnomAD4 genome

AF:

0.0000131

AC:

AN:

152334

Hom.:

Cov.:

AF XY:

0.00

AC XY:

AN XY:

74480

show subpopulations

African (AFR)

AF:

0.00

AC:

AN:

41584

American (AMR)

AF:

0.00

AC:

AN:

15314

Ashkenazi Jewish (ASJ)

AF:

0.00

AC:

AN:

3472

East Asian (EAS)

AF:

0.00

AC:

AN:

5168

South Asian (SAS)

AF:

0.00

AC:

AN:

4832

European-Finnish (FIN)

AF:

0.00

AC:

AN:

10626

Middle Eastern (MID)

AF:

0.00

AC:

AN:

292

European-Non Finnish (NFE)

AF:

0.0000294

AC:

AN:

68020

Other (OTH)

AF:

0.00

AC:

AN:

2114

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

Alfa

AF:

0.00

Hom.:

Bravo

AF:

0.00000378

ExAC

AF:

0.0000490

AC:

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

AlphaMissense

Benign

0.16

BayesDel_addAF

Benign

-0.40

BayesDel_noAF

Benign

-0.61

CADD

Benign

(source)

DANN

Benign

0.90

DEOGEN2

Benign

0.17

T;.

Eigen

Benign

-0.87

Eigen_PC

Benign

-0.99

FATHMM_MKL

Benign

0.12

LIST_S2

Benign

0.51

T;T

M_CAP

Benign

0.045

MetaRNN

Benign

0.015

T;T

MetaSVM

Benign

-1.1

PhyloP100

-0.24

PrimateAI

Uncertain

0.56

PROVEAN

Benign

-0.64

N;N

REVEL

Benign

0.016

Sift

Uncertain

0.0090

D;D

Sift4G

Benign

0.20

T;T

Polyphen

0.43

B;.

Vest4

0.14

MutPred

0.20

Gain of methylation at R301 (P = 0.0244);.;

MVP

0.13

MPC

0.30

ClinPred

0.065

GERP RS

1.1

Varity_R

0.083

gMVP

0.18

Mutation Taster

=100/0

polymorphism

(source)

Splicing

Name

Calibrated prediction

Score

Prediction

SpliceAI score (max)

0.010

Details are displayed if max score is > 0.2

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

Publications

You must be logged in to view publications. This limit was set because tens of millions (!) of queries from AI bots are generated daily.

1-206909808-C-T

Variant summary

Frequency

Consequence

Scores

Clinical Significance

Conservation

Publications

ACMG classification

Transcripts

RefSeq

Ensembl

Frequencies

Age Distribution

ClinVar

Computational scores

Splicing

Publications

Other links and lift over