chr1-161726853-C-T

Variant names:

• chr1-161726853-C-T
• NM_001002901.4:c.725C>T

Variant summary

Our verdict is Likely benign. The variant received -2 ACMG points: 2P and 4B. PM2 BP4_Strong

The NM_001002901.4(FCRLB):​c.725C>T​(p.Ala242Val) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.000000703 in 1,422,554 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a benign outcome for this variant. 14/21 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: 7.0e-7 (0 hom.)
• Consequence: FCRLB NM_001002901.4 missense
• Clinical Significance: Uncertain significance criteria provided, single submitter U:1
• Conservation: PhyloP100: -0.125
• 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: Likely_benign. The variant received -2 ACMG points.

• PM2: Very rare variant in population databases, with high coverage
• BP4: Computational evidence support a benign effect (MetaRNN=0.047382146).

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.725C>T	p.Ala242Val	missense	Exon 7 of 8	NP_001002901.1	Q6BAA4-1
	FCRLB	NM_001320241.1		c.725C>T	p.Ala242Val	missense	Exon 6 of 7	NP_001307170.1	Q6BAA4-1
	FCRLB	NM_001288829.1		c.580C>T	p.Arg194Trp	missense	Exon 5 of 6	NP_001275758.1	Q6BAA4-4

Ensembl Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	FCRLB	ENST00000367948.7	TSL:1 MANE Select	c.725C>T	p.Ala242Val	missense	Exon 7 of 8	ENSP00000356925.2	Q6BAA4-1
	FCRLB	ENST00000367946.7	TSL:1	c.580C>T	p.Arg194Trp	missense	Exon 5 of 6	ENSP00000356923.3	Q6BAA4-4
	FCRLB	ENST00000367945.5	TSL:1	c.559C>T	p.Arg187Trp	missense	Exon 4 of 5	ENSP00000356922.1	Q6BAA4-5

Frequencies

GnomAD3 genomes Cov.: 32

GnomAD4 exome AF: 7.03e-7 AC: 1 AN: 1422554 Hom.: 0 Cov.: 30 AF XY: 0.00000142 AC XY: 1 AN XY: 704336

African (AFR) AF: 0.0000310 AC: 1 AN: 32298

American (AMR) AF: 0.00 AC: 0 AN: 39846

Ashkenazi Jewish (ASJ) AF: 0.00 AC: 0 AN: 25350

East Asian (EAS) AF: 0.00 AC: 0 AN: 37406

South Asian (SAS) AF: 0.00 AC: 0 AN: 81962

European-Finnish (FIN) AF: 0.00 AC: 0 AN: 49936

Middle Eastern (MID) AF: 0.00 AC: 0 AN: 4804

European-Non Finnish (NFE) AF: 0.00 AC: 0 AN: 1092300

Other (OTH) AF: 0.00 AC: 0 AN: 58652

GnomAD4 genome Cov.: 32

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	Benign	0.081
BayesDel_addAF	Benign	-0.055	T
BayesDel_noAF	Benign	-0.32
CADD	Benign	8.8
DANN	Uncertain	0.98
DEOGEN2	Benign	0.025	T
Eigen	Benign	-1.2
Eigen_PC	Benign	-1.1
FATHMM_MKL	Benign	0.0090	N
LIST_S2	Benign	0.40	T
M_CAP	Benign	0.016	T
MetaRNN	Benign	0.047	T
MetaSVM	Benign	-0.91	T
PhyloP100		-0.13
PrimateAI	Uncertain	0.54	T
PROVEAN	Benign	0.40	N
REVEL	Benign	0.18
Sift	Benign	0.25	T
Sift4G	Benign	0.22	T
Polyphen		0.0020	B
Vest4		0.042
MutPred		0.39		Gain of MoRF binding (P = 0.1298)
MVP		0.41
MPC		0.70
ClinPred		0.045	T
GERP RS		1.5
Varity_R		0.028
gMVP		0.17
Mutation Taster		=99/1	polymorphism

Splicing

Name	Calibrated prediction	Score	Prediction
SpliceAI score (max)		0.010		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

hg19: chr1-161696643;