ENST00000628511.2:c.856C>G

Variant names:

• chr1-206909519-G-C
• rs918093286
• ENST00000628511.2:c.856C>G

Variant summary

Our verdict is Uncertain significance. The variant received 0 ACMG points: 2P and 2B. PM2 BP4_Moderate

The ENST00000628511.2(FCMR):​c.856C>G​(p.His286Asp) variant causes a missense, splice region change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.000000853 in 1,172,102 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a benign outcome for this variant. 13/16 in silico tools predict a benign outcome for this variant. 3/3 splice prediction tools predict no significant impact on normal splicing. 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. H286Y) has been classified as Likely benign.

• Frequency:
  • Genomes: not found (cov: 32)
  • Exomes 𝑓: 8.5e-7 (0 hom.)
• Consequence: FCMR ENST00000628511.2 missense, splice_region
• Scores: Splicing: ADA: 0.00005530
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.453
• 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: 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=0.13460457).

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
FCMR	NM_005449.5	c.987C>G	p.Gly329Gly	splice_region_variant, synonymous_variant	Exon 7 of 8	ENST00000367091.8	NP_005440.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
FCMR	ENST00000367091.8	c.987C>G	p.Gly329Gly	splice_region_variant, synonymous_variant	Exon 7 of 8	1	NM_005449.5	ENSP00000356058.3

Frequencies

GnomAD3 genomes Cov.: 32

GnomAD4 exome AF: 8.53e-7 AC: 1 AN: 1172102 Hom.: 0 Cov.: 30 AF XY: 0.00 AC XY: 0 AN XY: 562086

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

African (AFR) AF: 0.00 AC: 0 AN: 23402

American (AMR) AF: 0.00 AC: 0 AN: 8868

Ashkenazi Jewish (ASJ) AF: 0.00 AC: 0 AN: 16530

East Asian (EAS) AF: 0.0000373 AC: 1 AN: 26796

South Asian (SAS) AF: 0.00 AC: 0 AN: 43992

European-Finnish (FIN) AF: 0.00 AC: 0 AN: 27772

Middle Eastern (MID) AF: 0.00 AC: 0 AN: 4090

European-Non Finnish (NFE) AF: 0.00 AC: 0 AN: 972592

Other (OTH) AF: 0.00 AC: 0 AN: 48060

⚠️ The allele balance in gnomAD4 Exomes is highly skewed from 0.5 (p-value = 0.000000), which strongly suggests a high chance of mosaicism in these individuals.

GnomAD4 genome Cov.: 32

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_addAF	Benign	-0.41	T
BayesDel_noAF	Benign	-0.82
CADD	Benign	1.9
DANN	Benign	0.87
Eigen	Benign	-0.055
Eigen_PC	Benign	-0.50
FATHMM_MKL	Benign	0.075	N
LIST_S2	Benign	0.19	T
M_CAP	Benign	0.0099	T
MetaRNN	Benign	0.13	T
MetaSVM	Benign	-1.0	T
PhyloP100		-0.45
Sift4G	Benign	0.61	T
Vest4		0.14
MVP		0.34
ClinPred		0.032	T
GERP RS		-1.7
Mutation Taster		=88/12	polymorphism

Splicing

Name	Calibrated prediction	Score	Prediction
dbscSNV1_ADA	Benign	0.000055
dbscSNV1_RF	Benign	0.0040
SpliceAI score (max)		0.030		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: rs918093286; hg19: chr1-207082864;