Genetic Variant FCAMR:p.Gly475Ala (chr1-206960452-C-G) – 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_001170631.2(FCAMR):c.1424G>C(p.Gly475Ala) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00000131 in 1,520,916 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a benign outcome for this variant. 15/20 in silico tools predict a benign outcome for this variant. Variant has been reported in ClinVar as Uncertain significance (★).

Frequency

Genomes: 𝑓 0.0000066 ( 0 hom., cov: 32)

Exomes 𝑓: 7.3e-7 ( 0 hom. )

Consequence

FCAMR
NM_001170631.2 missense

Scores

Clinical Significance

Uncertain significance criteria provided, single submitter U:1

Conservation

PhyloP100: -0.00900

Publications

0 publications found

Variant links:

Genes affected

FCAMR (HGNC:24692): (Fc alpha and mu receptor) Predicted to enable IgA binding activity; IgM binding activity; and transmembrane signaling receptor activity. Predicted to be involved in adaptive immune response. Predicted to be integral component of membrane. Predicted to be active in plasma membrane. [provided by Alliance of Genome Resources, Apr 2022]

FCAMR links:

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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=0.04348874).

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_001170631.2. You can select a different transcript below to see updated ACMG assignments.

RefSeq Transcripts

Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
FCAMR	NM_001170631.2	MANE Select	c.1424G>C	p.Gly475Ala	missense	Exon 6 of 8	NP_001164102.1	Q8WWV6-6
FCAMR	NM_001424868.1		c.1289G>C	p.Gly430Ala	missense	Exon 4 of 6	NP_001411797.1	Q8WWV6-1
FCAMR	NM_001122979.3		c.653-655G>C		intron	N/A	NP_001116451.1	A0AB56DZ37

Ensembl Transcripts

Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
FCAMR	ENST00000324852.9	TSL:2 MANE Select	c.1424G>C	p.Gly475Ala	missense	Exon 6 of 8	ENSP00000316491.4	Q8WWV6-6
FCAMR	ENST00000450945.3	TSL:1	c.653-655G>C		intron	N/A	ENSP00000392707.2	A0AB56DZ37
FCAMR	ENST00000486178.1	TSL:1	n.384G>C		non_coding_transcript_exon	Exon 1 of 2

Frequencies

GnomAD3 genomes

AF:

0.00000657

AC:

AN:

152188

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:

0.00316

Gnomad NFE

AF:

0.00

Gnomad OTH

AF:

0.00

GnomAD4 exome

AF:

7.31e-7

AC:

AN:

1368610

Hom.:

Cov.:

AF XY:

0.00

AC XY:

AN XY:

671938

show subpopulations

African (AFR)

AF:

0.00

AC:

AN:

30540

American (AMR)

AF:

0.00

AC:

AN:

31888

Ashkenazi Jewish (ASJ)

AF:

0.00

AC:

AN:

23108

East Asian (EAS)

AF:

0.00

AC:

AN:

35454

South Asian (SAS)

AF:

0.00

AC:

AN:

73570

European-Finnish (FIN)

AF:

0.00

AC:

AN:

48308

Middle Eastern (MID)

AF:

0.00

AC:

AN:

4394

European-Non Finnish (NFE)

AF:

9.39e-7

AC:

AN:

1064852

Other (OTH)

AF:

0.00

AC:

AN:

56496

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.525

Heterozygous variant carriers

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

GnomAD4 genome

AF:

0.00000657

AC:

AN:

152306

Hom.:

Cov.:

AF XY:

0.0000134

AC XY:

AN XY:

74468

show subpopulations

African (AFR)

AF:

0.00

AC:

AN:

41580

American (AMR)

AF:

0.00

AC:

AN:

15304

Ashkenazi Jewish (ASJ)

AF:

0.00

AC:

AN:

3472

East Asian (EAS)

AF:

0.00

AC:

AN:

5172

South Asian (SAS)

AF:

0.00

AC:

AN:

4824

European-Finnish (FIN)

AF:

0.00

AC:

AN:

10616

Middle Eastern (MID)

AF:

0.00340

AC:

AN:

294

European-Non Finnish (NFE)

AF:

0.00

AC:

AN:

68018

Other (OTH)

AF:

0.00

AC:

AN:

2114

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.425

Heterozygous variant carriers

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Alfa

AF:

0.00

Hom.:

Bravo

AF:

0.00000756

ClinVar

ClinVar submissions

Significance:Uncertain significance

Revision:criteria provided, single submitter

View on ClinVar

Pathogenic

VUS

Benign

Condition

not specified (1)

Computational scores

Source: dbNSFP v4.9

Name

Calibrated prediction

Score

Prediction

AlphaMissense

Benign

0.13

BayesDel_addAF

Benign

-0.41

BayesDel_noAF

Benign

-0.83

CADD

Benign

3.4

(source)

DANN

Benign

0.44

DEOGEN2

Benign

0.021

Eigen

Benign

-1.1

Eigen_PC

Benign

-1.1

FATHMM_MKL

Benign

0.083

LIST_S2

Benign

0.28

M_CAP

Benign

0.0052

MetaRNN

Benign

0.043

MetaSVM

Benign

-0.92

PhyloP100

-0.0090

PrimateAI

Benign

0.29

PROVEAN

Benign

-0.74

REVEL

Benign

0.099

Sift

Benign

0.63

Sift4G

Benign

0.71

Vest4

0.059

MVP

0.081

MPC

0.17

ClinPred

0.048

GERP RS

1.6

gMVP

0.092

Mutation Taster

=98/2

polymorphism

(source)

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

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Variant summary

Frequency

Consequence

Scores

Clinical Significance

Conservation

Publications

ACMG classification

Variant Effect in Transcripts

RefSeq Transcripts

Ensembl Transcripts

Frequencies

ClinVar

Computational scores

Splicing

Publications

Other links and lift over