chr1-161710489-G-A

Position:

• chr1-161710489-G-A

Variant summary

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

The NM_001184866.2(FCRLA):​c.94G>A​(p.Ala32Thr) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant was absent in control chromosomes in GnomAD project. In-silico tool predicts a benign outcome for this variant. 13/18 in silico tools predict a benign outcome for this variant. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar.

• Frequency: Genomes: not found (cov: 31)
• Consequence: FCRLA NM_001184866.2 missense
• Clinical Significance: Uncertain significance criteria provided, single submitter U:1
• Conservation: PhyloP100: 0.986

Genes affected

FCRLA (HGNC:18504): (Fc receptor like A) This gene encodes a protein similar to receptors for the Fc fragment of gamma immunoglobulin (IgG). These receptors, referred to as FCGRs, mediate the destruction of IgG-coated antigens and of cells induced by antibodies. This encoded protein is selectively expressed in B cells, and may be involved in their development. This protein may also be involved in the development of lymphomas. Multiple alternatively spliced transcript variants that encode different protein isoforms have been described for this gene. [provided by RefSeq, Aug 2011]

FCRLA (HGNC:):

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=0.082871884).

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
FCRLA	NM_032738.4	c.80-271G>A		intron_variant		ENST00000236938.12	NP_116127.4

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
FCRLA	ENST00000236938.12	c.80-271G>A		intron_variant		1	NM_032738.4	ENSP00000236938.7

Frequencies

GnomAD3 genomes Cov.: 31

GnomAD3 exomes AF: 0.00000662 AC: 1 AN: 150946 Hom.: 0 AF XY: 0.00 AC XY: 0 AN XY: 80870

Gnomad AFR exome AF: 0.00

Gnomad AMR exome AF: 0.00

Gnomad ASJ exome AF: 0.00

Gnomad EAS exome AF: 0.00

Gnomad SAS exome AF: 0.00

Gnomad FIN exome AF: 0.00

Gnomad NFE exome AF: 0.0000178

Gnomad OTH exome AF: 0.00

GnomAD4 exome Cov.: 34

GnomAD4 genome Cov.: 31

Alfa AF: 0.0000936 Hom.: 0

Bravo AF: 0.00000756

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

Nov 15, 2024

The c.145G>A (p.A49T) alteration is located in exon 2 (coding exon 2) of the FCRLA gene. This alteration results from a G to A substitution at nucleotide position 145, causing the alanine (A) at amino acid position 49 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
BayesDel_addAF	Benign	-0.31	T
BayesDel_noAF	Benign	-0.69
CADD	Benign	16
DANN	Benign	0.92
Eigen	Benign	-0.66
Eigen_PC	Benign	-0.53
FATHMM_MKL	Benign	0.64	D
LIST_S2	Benign	0.53	T;T;T;T
M_CAP	Benign	0.0092	T
MetaRNN	Benign	0.080	T;T;T;T
MetaSVM	Benign	-0.88	T
PrimateAI	Benign	0.32	T
PROVEAN	Benign	-0.36	N;N;N;N
REVEL	Benign	0.015
Sift	Uncertain	0.015	D;T;T;D
Sift4G	Benign	0.13	T;T;T;T
Vest4		0.14
MutPred		0.40		Gain of phosphorylation at A49 (P = 0.2244);Gain of phosphorylation at A49 (P = 0.2244);.;.;
MVP		0.19
MPC		0.029
ClinPred		0.099	T
GERP RS		2.3
gMVP		0.090

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: rs1193366248; hg19: chr1-161680279;