1-157802664-C-G

Position:

• chr1-157802664-C-G

Variant summary

Our verdict is Uncertain significance. Variant got 1 ACMG points: 2P and 1B. PM2 BP4

The NM_052938.5(FCRL1):​c.320G>C​(p.Arg107Thr) variant causes a missense, splice region change. The variant was absent in control chromosomes in GnomAD project. In-silico tool predicts a benign outcome for this variant. 2/3 splice prediction tools predict no significant impact on normal splicing. Variant has been reported in ClinVar as Uncertain significance (★).

• Frequency: Genomes: not found (cov: 32)
• Consequence: FCRL1 NM_052938.5 missense, splice_region
• Scores: Splicing: ADA: 0.8435
• Clinical Significance: Uncertain significance criteria provided, single submitter U:1
• Conservation: PhyloP100: 4.11

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 1 ACMG points.

• PM2: Very rare variant in population databases, with high coverage
• BP4: Computational evidence support a benign effect (MetaRNN=0.3535536).

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
FCRL1	NM_052938.5	c.320G>C	p.Arg107Thr	missense_variant, splice_region_variant	4/11	ENST00000368176.8	NP_443170.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
FCRL1	ENST00000368176.8	c.320G>C	p.Arg107Thr	missense_variant, splice_region_variant	4/11	1	NM_052938.5	ENSP00000357158.3

Frequencies

GnomAD3 genomes Cov.: 32

GnomAD4 exome Cov.: 33

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

Jun 05, 2023

The c.320G>C (p.R107T) alteration is located in exon 4 (coding exon 4) of the FCRL1 gene. This alteration results from a G to C substitution at nucleotide position 320, causing the arginine (R) at amino acid position 107 to be replaced by a threonine (T). 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	Benign	0.21
BayesDel_addAF	Benign	-0.20	T
BayesDel_noAF	Benign	-0.52
CADD	Uncertain	25
DANN	Benign	0.95
DEOGEN2	Benign	0.070	.;T;.
Eigen	Benign	0.070
Eigen_PC	Benign	0.023
FATHMM_MKL	Uncertain	0.93	D
LIST_S2	Uncertain	0.87	D;D;D
M_CAP	Benign	0.0056	T
MetaRNN	Benign	0.35	T;T;T
MetaSVM	Benign	-1.0	T
MutationAssessor	Benign	1.9	L;L;L
PrimateAI	Benign	0.30	T
PROVEAN	Pathogenic	-4.4	D;D;D
REVEL	Benign	0.23
Sift	Benign	0.033	D;T;T
Sift4G	Benign	0.25	T;T;T
Polyphen		0.99	D;P;D
Vest4		0.35
MutPred		0.54		Loss of MoRF binding (P = 0.0365);Loss of MoRF binding (P = 0.0365);Loss of MoRF binding (P = 0.0365);
MVP		0.68
MPC		0.42
ClinPred		0.82	D
GERP RS		4.5
Varity_R		0.12
gMVP		0.37

Splicing

Name	Calibrated prediction	Score	Prediction
dbscSNV1_ADA	Benign	0.84
dbscSNV1_RF	Benign	0.65
SpliceAI score (max)		0.31		Details are displayed if max score is > 0.2
DS_AG_spliceai		0.31		Position offset: 31
DS_DG_spliceai		0.20		Position offset: -49

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: chr1-157772454;