rs34868416

Variant names:

• chr1-161727529-G-A
• rs34868416
• NM_001002901.4:c.1148G>A

Variant summary

Our verdict is Benign. The variant received -12 ACMG points: 0P and 12B. BP4_Strong BA1

The NM_001002901.4(FCRLB):​c.1148G>A​(p.Gly383Asp) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0802 in 1,614,042 control chromosomes in the GnomAD database, including 5,569 homozygotes. In-silico tool predicts a benign outcome for this variant. 13/21 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: 𝑓 0.062 (381 hom., cov: 31)
  • Exomes 𝑓: 0.082 (5188 hom.)
• Consequence: FCRLB NM_001002901.4 missense
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 2.21
• Publications: 13 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: Benign. The variant received -12 ACMG points.

• BP4: Computational evidence support a benign effect (MetaRNN=0.0016637743).
• BA1: GnomAd4 highest subpopulation (NFE) allele frequency at 95% confidence interval = 0.0836 is higher than 0.05.

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.1148G>A	p.Gly383Asp	missense	Exon 8 of 8	NP_001002901.1	Q6BAA4-1
	FCRLB	NM_001320241.1		c.1148G>A	p.Gly383Asp	missense	Exon 7 of 7	NP_001307170.1	Q6BAA4-1
	FCRLB	NM_001288829.1		c.*46G>A		3_prime_UTR	Exon 6 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.1148G>A	p.Gly383Asp	missense	Exon 8 of 8	ENSP00000356925.2	Q6BAA4-1
	FCRLB	ENST00000367946.7	TSL:1	c.*46G>A		3_prime_UTR	Exon 6 of 6	ENSP00000356923.3	Q6BAA4-4
	FCRLB	ENST00000367945.5	TSL:1	c.*46G>A		3_prime_UTR	Exon 5 of 5	ENSP00000356922.1	Q6BAA4-5

Frequencies

GnomAD3 genomes AF: 0.0618 AC: 9401 AN: 152038 Hom.: 380 Cov.: 31

Gnomad AFR AF: 0.0175

Gnomad AMI AF: 0.0186

Gnomad AMR AF: 0.0682

Gnomad ASJ AF: 0.0715

Gnomad EAS AF: 0.0789

Gnomad SAS AF: 0.0511

Gnomad FIN AF: 0.0708

Gnomad MID AF: 0.0475

Gnomad NFE AF: 0.0854

Gnomad OTH AF: 0.0690

GnomAD2 exomes AF: 0.0734 AC: 18377 AN: 250496 AF XY: 0.0734

Gnomad AFR exome AF: 0.0160

Gnomad AMR exome AF: 0.0743

Gnomad ASJ exome AF: 0.0764

Gnomad EAS exome AF: 0.0776

Gnomad FIN exome AF: 0.0695

Gnomad NFE exome AF: 0.0872

Gnomad OTH exome AF: 0.0802

GnomAD4 exome AF: 0.0821 AC: 120033 AN: 1461886 Hom.: 5188 Cov.: 34 AF XY: 0.0808 AC XY: 58776 AN XY: 727244

African (AFR) AF: 0.0144 AC: 481 AN: 33480

American (AMR) AF: 0.0727 AC: 3252 AN: 44724

Ashkenazi Jewish (ASJ) AF: 0.0716 AC: 1871 AN: 26136

East Asian (EAS) AF: 0.0974 AC: 3865 AN: 39700

South Asian (SAS) AF: 0.0486 AC: 4196 AN: 86258

European-Finnish (FIN) AF: 0.0733 AC: 3915 AN: 53416

Middle Eastern (MID) AF: 0.0437 AC: 252 AN: 5768

European-Non Finnish (NFE) AF: 0.0878 AC: 97673 AN: 1112008

Other (OTH) AF: 0.0750 AC: 4528 AN: 60396

GnomAD4 genome AF: 0.0618 AC: 9397 AN: 152156 Hom.: 381 Cov.: 31 AF XY: 0.0611 AC XY: 4543 AN XY: 74382

African (AFR) AF: 0.0174 AC: 723 AN: 41542

American (AMR) AF: 0.0681 AC: 1042 AN: 15292

Ashkenazi Jewish (ASJ) AF: 0.0715 AC: 248 AN: 3470

East Asian (EAS) AF: 0.0792 AC: 407 AN: 5136

South Asian (SAS) AF: 0.0508 AC: 244 AN: 4806

European-Finnish (FIN) AF: 0.0708 AC: 751 AN: 10606

Middle Eastern (MID) AF: 0.0408 AC: 12 AN: 294

European-Non Finnish (NFE) AF: 0.0854 AC: 5809 AN: 67988

Other (OTH) AF: 0.0682 AC: 144 AN: 2110

Alfa AF: 0.0789 Hom.: 1713

Bravo AF: 0.0611

TwinsUK AF: 0.0914 AC: 339

ALSPAC AF: 0.0991 AC: 382

ESP6500AA AF: 0.0161 AC: 71

ESP6500EA AF: 0.0883 AC: 759

ExAC AF: 0.0713 AC: 8659

Asia WGS AF: 0.0800 AC: 276 AN: 3478

EpiCase AF: 0.0833

EpiControl AF: 0.0847

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
AlphaMissense	Benign	0.095
BayesDel_addAF	Benign	-0.64	T
BayesDel_noAF	Benign	-0.58
CADD	Benign	21
DANN	Uncertain	1.0
DEOGEN2	Benign	0.048	T
Eigen	Benign	0.074
Eigen_PC	Benign	0.027
FATHMM_MKL	Benign	0.53	D
LIST_S2	Benign	0.52	T
MetaRNN	Benign	0.0017	T
MetaSVM	Benign	-0.81	T
MutationAssessor	Uncertain	2.1	M
PhyloP100		2.2
PrimateAI	Benign	0.41	T
PROVEAN	Benign	-1.7	N
REVEL	Benign	0.080
Sift	Benign	0.056	T
Sift4G	Benign	0.16	T
Polyphen		0.96	D
Vest4		0.072
MPC		0.99
ClinPred		0.073	T
GERP RS		2.4
Varity_R		0.19
gMVP		0.48
Mutation Taster		=100/0	polymorphism (auto)

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: rs34868416; hg19: chr1-161697319; COSMIC: COSV61059268;