1-157802041-C-G

Position:

• chr1-157802041-C-G

Variant summary

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

The NM_052938.5(FCRL1):​c.760G>C​(p.Ala254Pro) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant was absent in control chromosomes in GnomAD project. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar.

• Frequency: Genomes: not found (cov: 32)
• Consequence: FCRL1 NM_052938.5 missense
• Clinical Significance: Uncertain significance criteria provided, single submitter U:1
• Conservation: PhyloP100: 1.75

Genes affected

FCRL1 (HGNC:18509): (Fc receptor like 1) This gene encodes a member of the immunoglobulin receptor superfamily and is one of several Fc receptor-like glycoproteins clustered on the long arm of chromosome 1. The encoded protein contains three extracellular C2-like immunoglobulin domains, a transmembrane domain and a cytoplasmic domain with two immunoreceptor-tyrosine activation motifs. This protein may play a role in the regulation of cancer cell growth. Alternative splicing results in multiple transcript variants. [provided by RefSeq, Apr 2009]

FCRL1 (HGNC:):

ACMG classification

Verdict is Uncertain_significance. Variant got 2 ACMG points.

• PM2: Very rare variant in population databases, with high coverage

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
FCRL1	NM_052938.5	c.760G>C	p.Ala254Pro	missense_variant	5/11	ENST00000368176.8	NP_443170.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
FCRL1	ENST00000368176.8	c.760G>C	p.Ala254Pro	missense_variant	5/11	1	NM_052938.5	ENSP00000357158.3

Frequencies

GnomAD3 genomes Cov.: 32

GnomAD4 exome Cov.: 32

GnomAD4 genome Cov.: 32

ClinVar

Significance: Uncertain significance

Submissions summary: Uncertain:1

Revision: criteria provided, single submitter

Submissions by phenotype

not specified Uncertain:1

Uncertain significance, criteria provided, single submitter

clinical testing

Ambry Genetics

Aug 28, 2024

The c.760G>C (p.A254P) alteration is located in exon 5 (coding exon 5) of the FCRL1 gene. This alteration results from a G to C substitution at nucleotide position 760, causing the alanine (A) at amino acid position 254 to be replaced by a proline (P). 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
AlphaMissense	Uncertain	0.45
BayesDel_addAF	Benign	-0.11	T
BayesDel_noAF	Benign	-0.40
CADD	Benign	21
DANN	Uncertain	1.0
DEOGEN2	Benign	0.017	.;T;.
Eigen	Benign	0.16
Eigen_PC	Benign	-0.066
FATHMM_MKL	Benign	0.13	N
LIST_S2	Uncertain	0.95	D;D;D
M_CAP	Benign	0.0056	T
MetaRNN	Uncertain	0.45	T;T;T
MetaSVM	Benign	-1.0	T
MutationAssessor	Pathogenic	3.9	H;H;H
PrimateAI	Benign	0.35	T
PROVEAN	Pathogenic	-4.5	D;D;D
REVEL	Benign	0.11
Sift	Benign	0.039	D;D;D
Sift4G	Uncertain	0.032	D;D;D
Polyphen		1.0	D;D;D
Vest4		0.44
MutPred		0.44		Gain of glycosylation at A254 (P = 0.0153);Gain of glycosylation at A254 (P = 0.0153);Gain of glycosylation at A254 (P = 0.0153);
MVP		0.52
MPC		0.49
ClinPred		0.93	D
GERP RS		4.0
Varity_R		0.70
gMVP		0.47

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

No publications associated with this variant yet.

Other links and lift over

hg19: chr1-157771831;