chr1-206909855-C-A

Variant names:

• chr1-206909855-C-A
• rs1006346624
• ENST00000628511.2:c.724G>T

Variant summary

Our verdict is Likely benign. The variant received -1 ACMG points: 2P and 3B. PM2 BP4_Moderate BP7

The NM_005449.5(FCMR):​c.855G>T​(p.Arg285Arg) variant causes a synonymous change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.000000813 in 1,229,890 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. Synonymous variant affecting the same amino acid position (i.e. R285R) has been classified as Likely benign.

• Frequency:
  • Genomes: not found (cov: 32)
  • Exomes 𝑓: 8.1e-7 (0 hom.)
• Consequence: FCMR NM_005449.5 synonymous
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 0.00800
• Publications: 0 publications found

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]

ACMG classification

Our verdict: Likely_benign. The variant received -1 ACMG points.

• PM2: Very rare variant in population databases, with high coverage
• BP4: Computational evidence support a benign effect (MetaRNN=0.0945839).
• BP7: Synonymous conserved (PhyloP=0.008 with no splicing effect.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
FCMR	NM_005449.5	c.855G>T	p.Arg285Arg	synonymous_variant	Exon 6 of 8	ENST00000367091.8	NP_005440.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
FCMR	ENST00000367091.8	c.855G>T	p.Arg285Arg	synonymous_variant	Exon 6 of 8	1	NM_005449.5	ENSP00000356058.3

Frequencies

GnomAD3 genomes Cov.: 32

GnomAD4 exome AF: 8.13e-7 AC: 1 AN: 1229890 Hom.: 0 Cov.: 31 AF XY: 0.00000168 AC XY: 1 AN XY: 593864

African (AFR) AF: 0.00 AC: 0 AN: 23762

American (AMR) AF: 0.00 AC: 0 AN: 10768

Ashkenazi Jewish (ASJ) AF: 0.00 AC: 0 AN: 17424

East Asian (EAS) AF: 0.00 AC: 0 AN: 27224

South Asian (SAS) AF: 0.00 AC: 0 AN: 54732

European-Finnish (FIN) AF: 0.00 AC: 0 AN: 39288

Middle Eastern (MID) AF: 0.00 AC: 0 AN: 4684

European-Non Finnish (NFE) AF: 9.98e-7 AC: 1 AN: 1001588

Other (OTH) AF: 0.00 AC: 0 AN: 50420

GnomAD4 genome Cov.: 32

Alfa AF: 0.00 Hom.: 0

Bravo AF: 0.00000378

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_addAF	Benign	-0.30	T
BayesDel_noAF	Benign	-0.67
CADD	Benign	9.0
DANN	Uncertain	0.99
Eigen	Benign	-0.77
Eigen_PC	Benign	-0.94
FATHMM_MKL	Benign	0.18	N
LIST_S2	Benign	0.35	T
M_CAP	Benign	0.0058	T
MetaRNN	Benign	0.095	T
MetaSVM	Benign	-0.98	T
PhyloP100		0.0080
Sift4G	Uncertain	0.011	D
Vest4		0.23
MVP		0.19
ClinPred		0.088	T
GERP RS		-0.25
Mutation Taster		=99/1	polymorphism

Splicing

Name	Calibrated prediction	Score	Prediction
SpliceAI score (max)		0.050		Details are displayed if max score is > 0.2

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

Other links and lift over

dbSNP: rs1006346624; hg19: chr1-207083200;