rs1891019

Variant names:

• chr1-161721643-C-T
• rs1891019
• NM_001002901.4:c.-135C>T

Variant summary

Our verdict is Benign. Variant got -12 ACMG points: 0P and 12B. BP4_Strong BA1

The NM_001002901.4(FCRLB):​c.-135C>T variant causes a 5 prime UTR premature start codon gain change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.627 in 152,050 control chromosomes in the GnomAD database, including 32,027 homozygotes. In-silico tool predicts a benign outcome for this variant. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar.

• Frequency:
  • Genomes: 𝑓 0.63 (32025 hom., cov: 32)
  • Exomes 𝑓: 0.70 (2 hom.)
• Consequence: FCRLB NM_001002901.4 5_prime_UTR_premature_start_codon_gain
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.0190

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

Verdict is Benign. Variant got -12 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.86).
• BA1: GnomAd4 highest subpopulation (AMR) allele frequency at 95% confidence interval = 0.771 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
FCRLB	NM_001002901.4	c.-135C>T		5_prime_UTR_premature_start_codon_gain_variant	Exon 1 of 8	ENST00000367948.7	NP_001002901.1
FCRLB	NM_001002901.4	c.-135C>T		5_prime_UTR_variant	Exon 1 of 8	ENST00000367948.7	NP_001002901.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
FCRLB	ENST00000367948	c.-135C>T		5_prime_UTR_premature_start_codon_gain_variant	Exon 1 of 8	1	NM_001002901.4	ENSP00000356925.2
FCRLB	ENST00000367948	c.-135C>T		5_prime_UTR_variant	Exon 1 of 8	1	NM_001002901.4	ENSP00000356925.2

Frequencies

GnomAD3 genomes AF: 0.627 AC: 95231 AN: 151922 Hom.: 32008 Cov.: 32

Gnomad AFR AF: 0.373

Gnomad AMI AF: 0.484

Gnomad AMR AF: 0.782

Gnomad ASJ AF: 0.835

Gnomad EAS AF: 0.511

Gnomad SAS AF: 0.598

Gnomad FIN AF: 0.749

Gnomad MID AF: 0.750

Gnomad NFE AF: 0.727

Gnomad OTH AF: 0.694

GnomAD4 exome AF: 0.700 AC: 7 AN: 10 Hom.: 2 Cov.: 0 AF XY: 0.833 AC XY: 5 AN XY: 6

Gnomad4 FIN exome AF: 1.00

Gnomad4 NFE exome AF: 0.625

GnomAD4 genome AF: 0.627 AC: 95274 AN: 152040 Hom.: 32025 Cov.: 32 AF XY: 0.630 AC XY: 46807 AN XY: 74330

Gnomad4 AFR AF: 0.373

Gnomad4 AMR AF: 0.782

Gnomad4 ASJ AF: 0.835

Gnomad4 EAS AF: 0.510

Gnomad4 SAS AF: 0.600

Gnomad4 FIN AF: 0.749

Gnomad4 NFE AF: 0.727

Gnomad4 OTH AF: 0.695

Alfa AF: 0.718 Hom.: 79430

Bravo AF: 0.621

Asia WGS AF: 0.592 AC: 2062 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.86
CADD	Benign	2.8
DANN	Benign	0.68

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

Publications

LitVar

Other links and lift over

dbSNP: rs1891019; hg19: chr1-161691433;