1-157586742-G-A

Variant names:

• chr1-157586742-G-A
• rs2777963
• NM_031282.3:c.848-287C>T

Variant summary

Our verdict is Benign. The variant received -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
• Publications: 10 publications found

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

Our verdict: Benign. The variant received -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.

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_031282.3. You can select a different transcript below to see updated ACMG assignments.

RefSeq Transcripts

Selected	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	FCRL4	NM_031282.3	MANE Select	c.848-287C>T		intron	N/A	NP_112572.1

Ensembl Transcripts

Selected	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	FCRL4	ENST00000271532.2	TSL:1 MANE Select	c.848-287C>T		intron	N/A	ENSP00000271532.1
	FCRL4	ENST00000448509.6	TSL:2	n.589-287C>T		intron	N/A

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

African (AFR) AF: 0.691 AC: 28638 AN: 41446

American (AMR) AF: 0.811 AC: 12412 AN: 15306

Ashkenazi Jewish (ASJ) AF: 0.727 AC: 2520 AN: 3464

East Asian (EAS) AF: 0.909 AC: 4706 AN: 5176

South Asian (SAS) AF: 0.830 AC: 3997 AN: 4818

European-Finnish (FIN) AF: 0.786 AC: 8326 AN: 10590

Middle Eastern (MID) AF: 0.799 AC: 235 AN: 294

European-Non Finnish (NFE) AF: 0.762 AC: 51827 AN: 67984

Other (OTH) AF: 0.775 AC: 1636 AN: 2110

Alfa AF: 0.761 Hom.: 197064

Bravo AF: 0.752

Asia WGS AF: 0.884 AC: 3074 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.96
CADD	Benign	0.14
DANN	Benign	0.60
PhyloP100		-0.79
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: rs2777963; hg19: chr1-157556532;