rs2777963

Positions:

• chr1-157586742-G-A
• chr1-157586742-G-C
• chr1-157586742-G-T

Variant summary

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

The NM_031282.3(FCRL4):​c.848-287C>T variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.756 in 152,096 control chromosomes in the GnomAD database, including 43,730 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 0.76 (43730 hom., cov: 31)
• Consequence: FCRL4 NM_031282.3 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.792

Genes affected

FCRL4 (HGNC:18507): (Fc receptor like 4) This gene encodes a member of the immunoglobulin receptor superfamily and is one of several Fc receptor-like glycoproteins clustered on the long arm of chromosome 1. The encoded protein has four extracellular C2-type immunoglobulin domains, a transmembrane domain and a cytoplasmic domain that contains three immune-receptor tyrosine-based inhibitory motifs. This protein may play a role in the function of memory B-cells in the epithelia. Aberrations in the chromosomal region encoding this gene are associated with non-Hodgkin lymphoma and multiple myeloma. [provided by RefSeq, Apr 2009]

ACMG classification

Verdict is Benign. Variant got -12 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.96).
• BA1: GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.888 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
FCRL4	NM_031282.3	c.848-287C>T		intron_variant		ENST00000271532.2
FCRL4	XM_011510034.2	c.845-287C>T		intron_variant

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
FCRL4	ENST00000271532.2	c.848-287C>T		intron_variant		1	NM_031282.3	P1
FCRL4	ENST00000448509.6	n.589-287C>T		intron_variant, non_coding_transcript_variant		2

Frequencies

GnomAD3 genomes AF: 0.756 AC: 114932 AN: 151978 Hom.: 43678 Cov.: 31

Gnomad AFR AF: 0.690

Gnomad AMI AF: 0.813

Gnomad AMR AF: 0.811

Gnomad ASJ AF: 0.727

Gnomad EAS AF: 0.909

Gnomad SAS AF: 0.828

Gnomad FIN AF: 0.786

Gnomad MID AF: 0.807

Gnomad NFE AF: 0.762

Gnomad OTH AF: 0.775

We have no GnomAD4 exomes data on this position. Probably position not covered by the project.

GnomAD4 genome AF: 0.756 AC: 115035 AN: 152096 Hom.: 43730 Cov.: 31 AF XY: 0.762 AC XY: 56664 AN XY: 74360

Gnomad4 AFR AF: 0.691

Gnomad4 AMR AF: 0.811

Gnomad4 ASJ AF: 0.727

Gnomad4 EAS AF: 0.909

Gnomad4 SAS AF: 0.830

Gnomad4 FIN AF: 0.786

Gnomad4 NFE AF: 0.762

Gnomad4 OTH AF: 0.775

Alfa AF: 0.764 Hom.: 91580

Bravo AF: 0.752

Asia WGS AF: 0.884 AC: 3074 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.96
CADD	Benign	0.14
DANN	Benign	0.60

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: rs2777963; hg19: chr1-157556532;