1-206909828-G-A

Variant names:

• chr1-206909828-G-A
• rs528590548
• ENST00000628511.2:c.751C>T

Variant summary

Our verdict is Benign. The variant received -7 ACMG points: 0P and 7B. BP4_Strong BP6_Moderate BP7

The NM_005449.5(FCMR):​c.882C>T​(p.Arg294Arg) variant causes a synonymous change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0000114 in 1,402,240 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Likely benign (★).

• Frequency:
  • Genomes: 𝑓 0.000046 (0 hom., cov: 32)
  • Exomes 𝑓: 0.0000072 (0 hom.)
• Consequence: FCMR NM_005449.5 synonymous
• Clinical Significance: Likely benign criteria provided, single submitter B:1
• Conservation: PhyloP100: -0.0230
• 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: Benign. The variant received -7 ACMG points.

• BP4: Computational evidence support a benign effect (MetaRNN=0.040296584).
• BP6: Variant 1-206909828-G-A is Benign according to our data. Variant chr1-206909828-G-A is described in ClinVar as [Likely_benign]. Clinvar id is 3094145.Status of the report is criteria_provided_single_submitter, 1 stars.
• BP7: Synonymous conserved (PhyloP=-0.023 with no splicing effect.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
FCMR	NM_005449.5	c.882C>T	p.Arg294Arg	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.882C>T	p.Arg294Arg	synonymous_variant	Exon 6 of 8	1	NM_005449.5	ENSP00000356058.3

Frequencies

GnomAD3 genomes AF: 0.0000460 AC: 7 AN: 152210 Hom.: 0 Cov.: 32

Gnomad AFR AF: 0.00

Gnomad AMI AF: 0.00

Gnomad AMR AF: 0.000458

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: 0.00

Gnomad OTH AF: 0.00

GnomAD2 exomes AF: 0.00 AC: 0 AN: 18948 AF XY: 0.00

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: 0.00

Gnomad OTH exome AF: 0.00

GnomAD4 exome AF: 0.00000720 AC: 9 AN: 1249912 Hom.: 0 Cov.: 31 AF XY: 0.00000494 AC XY: 3 AN XY: 606940

African (AFR) AF: 0.00 AC: 0 AN: 24020

American (AMR) AF: 0.0000813 AC: 1 AN: 12302

Ashkenazi Jewish (ASJ) AF: 0.00 AC: 0 AN: 18002

East Asian (EAS) AF: 0.00 AC: 0 AN: 27772

South Asian (SAS) AF: 0.0000173 AC: 1 AN: 57740

European-Finnish (FIN) AF: 0.0000259 AC: 1 AN: 38614

Middle Eastern (MID) AF: 0.00 AC: 0 AN: 4694

European-Non Finnish (NFE) AF: 0.00000295 AC: 3 AN: 1015394

Other (OTH) AF: 0.0000584 AC: 3 AN: 51374

GnomAD4 genome AF: 0.0000460 AC: 7 AN: 152328 Hom.: 0 Cov.: 32 AF XY: 0.0000537 AC XY: 4 AN XY: 74482

African (AFR) AF: 0.00 AC: 0 AN: 41594

American (AMR) AF: 0.000457 AC: 7 AN: 15312

Ashkenazi Jewish (ASJ) AF: 0.00 AC: 0 AN: 3470

East Asian (EAS) AF: 0.00 AC: 0 AN: 5166

South Asian (SAS) AF: 0.00 AC: 0 AN: 4832

European-Finnish (FIN) AF: 0.00 AC: 0 AN: 10620

Middle Eastern (MID) AF: 0.00 AC: 0 AN: 292

European-Non Finnish (NFE) AF: 0.00 AC: 0 AN: 68014

Other (OTH) AF: 0.00 AC: 0 AN: 2116

Alfa AF: 0.00 Hom.: 0

Bravo AF: 0.000102

ClinVar

Significance: Likely benign

Submissions summary: Benign:1

Revision: criteria provided, single submitter

Submissions by phenotype

not specified Benign:1

Dec 09, 2023

Ambry Genetics

Significance: Likely benign

Review Status: criteria provided, single submitter

Collection Method: clinical testing

This alteration is classified as likely benign based on a combination of the following: seen in unaffected individuals, population frequency, intact protein function, lack of segregation with disease, co-occurrence, RNA analysis, in silico models, amino acid conservation, lack of disease association in case-control studies, and/or the mechanism of disease or impacted region is inconsistent with a known cause of pathogenicity. -

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_addAF	Benign	-0.36	T
BayesDel_noAF	Benign	-0.75
CADD	Benign	6.1
DANN	Uncertain	0.98
Eigen	Benign	-1.0
Eigen_PC	Benign	-1.2
FATHMM_MKL	Benign	0.092	N
LIST_S2	Benign	0.62	T
M_CAP	Benign	0.0071	T
MetaRNN	Benign	0.040	T
MetaSVM	Benign	-1.0	T
PhyloP100		-0.023
Sift4G	Benign	0.078	T
Vest4		0.28
MVP		0.12
ClinPred		0.11	T
GERP RS		-2.3
Mutation Taster		=99/1	polymorphism

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

Other links and lift over

dbSNP: rs528590548; hg19: chr1-207083173;