1-206960452-C-T

Variant names:

• chr1-206960452-C-T
• rs1425270586
• NM_001170631.2:c.1424G>A

Variant summary

Our verdict is Likely benign. The variant received -2 ACMG points: 2P and 4B. PM2 BP4_Strong

The NM_001170631.2(FCAMR):​c.1424G>A​(p.Gly475Glu) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00000292 in 1,368,610 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. 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. G475A) has been classified as Uncertain significance.

• Frequency:
  • Genomes: not found (cov: 32)
  • Exomes 𝑓: 0.0000029 (0 hom.)
• Consequence: FCAMR NM_001170631.2 missense
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.00900
• Publications: 0 publications found

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]

ACMG classification

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=0.06036043).

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

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	FCAMR	NM_001170631.2	MANE Select	c.1424G>A	p.Gly475Glu	missense	Exon 6 of 8	NP_001164102.1	Q8WWV6-6
	FCAMR	NM_001424868.1		c.1289G>A	p.Gly430Glu	missense	Exon 4 of 6	NP_001411797.1	Q8WWV6-1
	FCAMR	NM_001122979.3		c.653-655G>A		intron	N/A	NP_001116451.1	A0AB56DZ37

Ensembl Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	FCAMR	ENST00000324852.9	TSL:2 MANE Select	c.1424G>A	p.Gly475Glu	missense	Exon 6 of 8	ENSP00000316491.4	Q8WWV6-6
	FCAMR	ENST00000450945.3	TSL:1	c.653-655G>A		intron	N/A	ENSP00000392707.2	A0AB56DZ37
	FCAMR	ENST00000486178.1	TSL:1	n.384G>A		non_coding_transcript_exon	Exon 1 of 2

Frequencies

GnomAD3 genomes Cov.: 32

GnomAD4 exome AF: 0.00000292 AC: 4 AN: 1368610 Hom.: 0 Cov.: 30 AF XY: 0.00000298 AC XY: 2 AN XY: 671938

African (AFR) AF: 0.00 AC: 0 AN: 30540

American (AMR) AF: 0.00 AC: 0 AN: 31888

Ashkenazi Jewish (ASJ) AF: 0.00 AC: 0 AN: 23108

East Asian (EAS) AF: 0.00 AC: 0 AN: 35454

South Asian (SAS) AF: 0.00 AC: 0 AN: 73570

European-Finnish (FIN) AF: 0.00 AC: 0 AN: 48308

Middle Eastern (MID) AF: 0.00 AC: 0 AN: 4394

European-Non Finnish (NFE) AF: 0.00000376 AC: 4 AN: 1064852

Other (OTH) AF: 0.00 AC: 0 AN: 56496

GnomAD4 genome Cov.: 32

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
AlphaMissense	Benign	0.091
BayesDel_addAF	Benign	-0.37	T
BayesDel_noAF	Benign	-0.76
CADD	Benign	6.8
DANN	Benign	0.84
DEOGEN2	Benign	0.024	T
Eigen	Benign	-0.91
Eigen_PC	Benign	-0.92
FATHMM_MKL	Benign	0.030	N
LIST_S2	Benign	0.25	T
M_CAP	Benign	0.0047	T
MetaRNN	Benign	0.060	T
MetaSVM	Benign	-0.95	T
PhyloP100		-0.0090
PrimateAI	Benign	0.29	T
PROVEAN	Benign	-0.62	N
REVEL	Benign	0.069
Sift	Benign	0.24	T
Sift4G	Benign	0.74	T
Vest4		0.066
MVP		0.19
MPC		0.22
ClinPred		0.046	T
GERP RS		1.6
gMVP		0.077
Mutation Taster		=98/2	polymorphism

Splicing

Name	Calibrated prediction	Score	Prediction
SpliceAI score (max)		0.060		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: rs1425270586; hg19: chr1-207133797;