rs771484781

Variant names:

• chr1-206960701-G-A
• rs771484781
• NM_001170631.2:c.1175C>T

Variant summary

Our verdict is Uncertain significance. Variant got 0 ACMG points: 2P and 2B. PM2 BP4_Moderate

The NM_001170631.2(FCAMR):​c.1175C>T​(p.Pro392Leu) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00000143 in 1,399,914 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a benign outcome for this variant. 13/18 in silico tools predict a benign outcome for this variant. Variant has been reported in ClinVar as Uncertain significance (★).

• Frequency:
  • Genomes: not found (cov: 32)
  • Exomes 𝑓: 0.0000014 (0 hom.)
• Consequence: FCAMR NM_001170631.2 missense
• Clinical Significance: Uncertain significance criteria provided, single submitter U:1
• Conservation: PhyloP100: -1.53

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

Verdict is Uncertain_significance. Variant got 0 ACMG points.

• PM2: Very rare variant in population databases, with high coverage
• BP4: Computational evidence support a benign effect (MetaRNN=0.073245645).

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
FCAMR	NM_001170631.2	c.1175C>T	p.Pro392Leu	missense_variant	Exon 6 of 8	ENST00000324852.9	NP_001164102.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
FCAMR	ENST00000324852.9	c.1175C>T	p.Pro392Leu	missense_variant	Exon 6 of 8	2	NM_001170631.2	ENSP00000316491.4

Frequencies

GnomAD3 genomes Cov.: 32

GnomAD4 exome AF: 0.00000143 AC: 2 AN: 1399914 Hom.: 0 Cov.: 31 AF XY: 0.00000145 AC XY: 1 AN XY: 690440

Gnomad4 AFR exome AF: 0.0000316

Gnomad4 AMR exome AF: 0.00

Gnomad4 ASJ exome AF: 0.00

Gnomad4 EAS exome AF: 0.00

Gnomad4 SAS exome AF: 0.00

Gnomad4 FIN exome AF: 0.00

Gnomad4 NFE exome AF: 0.00

Gnomad4 OTH exome AF: 0.0000172

GnomAD4 genome Cov.: 32

Alfa AF: 0.0000282 Hom.: 0

Bravo AF: 0.0000151

TwinsUK AF: 0.00 AC: 0

ALSPAC AF: 0.000259 AC: 1

ClinVar

Significance: Uncertain significance

Submissions summary: Uncertain:1

Revision: criteria provided, single submitter

Submissions by phenotype

not specified Uncertain:1

Dec 30, 2024

Ambry Genetics

Significance: Uncertain significance

Review Status: criteria provided, single submitter

Collection Method: clinical testing

The c.1175C>T (p.P392L) alteration is located in exon 6 (coding exon 6) of the FCAMR gene. This alteration results from a C to T substitution at nucleotide position 1175, causing the proline (P) at amino acid position 392 to be replaced by a leucine (L). Based on insufficient or conflicting evidence, the clinical significance of this alteration remains unclear. -

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_addAF	Benign	-0.37	T
BayesDel_noAF	Benign	-0.77
CADD	Benign	1.2
DANN	Benign	0.64
DEOGEN2	Benign	0.016	T
Eigen	Benign	-1.5
Eigen_PC	Benign	-1.7
FATHMM_MKL	Benign	0.035	N
LIST_S2	Benign	0.55	T
M_CAP	Benign	0.0066	T
MetaRNN	Benign	0.073	T
MetaSVM	Benign	-1.0	T
PrimateAI	Benign	0.20	T
PROVEAN	Benign	-1.2	N
REVEL	Benign	0.039
Sift	Benign	0.14	T
Sift4G	Benign	0.25	T
Vest4		0.13
MVP		0.11
MPC		0.38
ClinPred		0.19	T
GERP RS		-10
gMVP		0.086

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

Publications

LitVar

Other links and lift over

dbSNP: rs771484781; hg19: chr1-207134046;