rs1683597975

Variant names:

• chr1-161726936-G-C
• rs1683597975
• NM_001002901.4:c.808G>C

Your query was ambiguous. Multiple possible variants found:

• chr1-161726936-G-C
• chr1-161726936-G-T

Variant summary

Our verdict is Uncertain significance. The variant received 2 ACMG points: 2P and 0B. PM2

The NM_001002901.4(FCRLB):​c.808G>C​(p.Ala270Pro) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.000000711 in 1,406,242 control chromosomes in the GnomAD database, with no homozygous occurrence. Variant has been reported in ClinVar as Uncertain significance (★).

• Frequency:
  • Genomes: not found (cov: 32)
  • Exomes 𝑓: 7.1e-7 (0 hom.)
• Consequence: FCRLB NM_001002901.4 missense
• Clinical Significance: Uncertain significance criteria provided, single submitter U:1
• Conservation: PhyloP100: 2.81
• Publications: 0 publications found

Genes affected

FCRLB (HGNC:26431): (Fc receptor like B) FCRL2 belongs to the Fc receptor family. Fc receptors are involved in phagocytosis, antibody-dependent cell cytotoxicity, immediate hypersensitivity, and transcytosis of immunoglobulins via their ability to bind immunoglobulin (Ig) constant regions (Chikaev et al., 2005 [PubMed 15676285]).[supplied by OMIM, Mar 2008]

ACMG classification

Our verdict: Uncertain_significance. The variant received 2 ACMG points.

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

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_001002901.4. 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
	FCRLB	NM_001002901.4	MANE Select	c.808G>C	p.Ala270Pro	missense	Exon 7 of 8	NP_001002901.1	Q6BAA4-1
	FCRLB	NM_001320241.1		c.808G>C	p.Ala270Pro	missense	Exon 6 of 7	NP_001307170.1	Q6BAA4-1
	FCRLB	NM_001288831.1		c.704G>C	p.Gly235Ala	missense	Exon 5 of 6	NP_001275760.1	Q6BAA4-2

Ensembl Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	FCRLB	ENST00000367948.7	TSL:1 MANE Select	c.808G>C	p.Ala270Pro	missense	Exon 7 of 8	ENSP00000356925.2	Q6BAA4-1
	FCRLB	ENST00000336830.9	TSL:1	c.704G>C	p.Gly235Ala	missense	Exon 5 of 6	ENSP00000338598.5	Q6BAA4-2
	FCRLB	ENST00000367944.3	TSL:1	c.683G>C	p.Gly228Ala	missense	Exon 4 of 5	ENSP00000356921.3	Q6BAA4-3

Frequencies

GnomAD3 genomes Cov.: 32

GnomAD4 exome AF: 7.11e-7 AC: 1 AN: 1406242 Hom.: 0 Cov.: 30 AF XY: 0.00 AC XY: 0 AN XY: 693572

African (AFR) AF: 0.00 AC: 0 AN: 31554

American (AMR) AF: 0.00 AC: 0 AN: 37144

Ashkenazi Jewish (ASJ) AF: 0.00 AC: 0 AN: 23396

East Asian (EAS) AF: 0.00 AC: 0 AN: 38308

South Asian (SAS) AF: 0.00 AC: 0 AN: 79852

European-Finnish (FIN) AF: 0.00 AC: 0 AN: 50490

Middle Eastern (MID) AF: 0.00 AC: 0 AN: 4884

European-Non Finnish (NFE) AF: 9.23e-7 AC: 1 AN: 1082980

Other (OTH) AF: 0.00 AC: 0 AN: 57634

GnomAD4 genome Cov.: 32

Alfa AF: 0.00 Hom.: 0

Bravo AF: 0.00000378

ClinVar

ClinVar submissions

Significance: Uncertain significance

Revision: criteria provided, single submitter

Pathogenic	VUS	Benign	Condition
-	1	-	not specified (1)

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
AlphaMissense	Pathogenic	0.98
BayesDel_addAF	Pathogenic	0.29	D
BayesDel_noAF	Pathogenic	0.18
CADD	Uncertain	24
DANN	Uncertain	1.0
DEOGEN2	Benign	0.19	T
Eigen	Benign	-0.25
Eigen_PC	Benign	-0.27
FATHMM_MKL	Benign	0.12	N
LIST_S2	Benign	0.57	T
M_CAP	Benign	0.045	D
MetaRNN	Uncertain	0.44	T
MetaSVM	Benign	-0.96	T
PhyloP100		2.8
PrimateAI	Pathogenic	0.80	T
PROVEAN	Benign	-2.3	N
REVEL	Pathogenic	0.67
Sift	Uncertain	0.0020	D
Sift4G	Uncertain	0.0070	D
Polyphen		0.91	P
Vest4		0.55
MutPred		0.36		Gain of disorder (P = 0.039)
MVP		0.60
MPC		0.98
ClinPred		0.98	D
GERP RS		3.7
Varity_R		0.49
gMVP		0.72
Mutation Taster		=93/7	polymorphism

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

Other links and lift over

dbSNP: rs1683597975; hg19: chr1-161696726;