1-206960921-T-A

Variant names:

• chr1-206960921-T-A
• rs976986132
• NM_001170631.2:c.955A>T

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.955A>T​(p.Met319Leu) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.000000714 in 1,400,014 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. M319T) has been classified as Uncertain significance.

• Frequency:
  • Genomes: not found (cov: 32)
  • Exomes 𝑓: 7.1e-7 (0 hom.)
• Consequence: FCAMR NM_001170631.2 missense
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -1.03
• 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=0.04965523).

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.955A>T	p.Met319Leu	missense	Exon 6 of 8	NP_001164102.1	Q8WWV6-6
	FCAMR	NM_001424868.1		c.820A>T	p.Met274Leu	missense	Exon 4 of 6	NP_001411797.1	Q8WWV6-1
	FCAMR	NM_001122979.3		c.653-1124A>T		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.955A>T	p.Met319Leu	missense	Exon 6 of 8	ENSP00000316491.4	Q8WWV6-6
	FCAMR	ENST00000450945.3	TSL:1	c.653-1124A>T		intron	N/A	ENSP00000392707.2	A0AB56DZ37
	FCAMR	ENST00000400962.8	TSL:5	c.653-1124A>T		intron	N/A	ENSP00000383746.3	A0AB56DZ37

Frequencies

GnomAD3 genomes Cov.: 32

GnomAD4 exome AF: 7.14e-7 AC: 1 AN: 1400014 Hom.: 0 Cov.: 31 AF XY: 0.00 AC XY: 0 AN XY: 690486

African (AFR) AF: 0.00 AC: 0 AN: 31600

American (AMR) AF: 0.00 AC: 0 AN: 35708

Ashkenazi Jewish (ASJ) AF: 0.00 AC: 0 AN: 25182

East Asian (EAS) AF: 0.00 AC: 0 AN: 35740

South Asian (SAS) AF: 0.00 AC: 0 AN: 79236

European-Finnish (FIN) AF: 0.00 AC: 0 AN: 49556

Middle Eastern (MID) AF: 0.00 AC: 0 AN: 5702

European-Non Finnish (NFE) AF: 9.27e-7 AC: 1 AN: 1079110

Other (OTH) AF: 0.00 AC: 0 AN: 58180

GnomAD4 genome Cov.: 32

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
AlphaMissense	Benign	0.13
BayesDel_addAF	Benign	-0.39	T
BayesDel_noAF	Benign	-0.79
CADD	Benign	0.038
DANN	Benign	0.72
DEOGEN2	Benign	0.014	T
Eigen	Benign	-1.7
Eigen_PC	Benign	-1.9
FATHMM_MKL	Benign	0.052	N
LIST_S2	Benign	0.31	T
M_CAP	Benign	0.0024	T
MetaRNN	Benign	0.050	T
MetaSVM	Benign	-1.0	T
PhyloP100		-1.0
PrimateAI	Benign	0.25	T
PROVEAN	Benign	-0.35	N
REVEL	Benign	0.020
Sift	Benign	0.17	T
Sift4G	Benign	0.42	T
Vest4		0.15
MVP		0.15
MPC		0.16
ClinPred		0.29	T
GERP RS		-9.8
gMVP		0.22
Mutation Taster		=98/2	polymorphism

Splicing

Name	Calibrated prediction	Score	Prediction
SpliceAI score (max)		0.020		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: rs976986132; hg19: chr1-207134266;