NM_031282.3:c.52+99C>T

Variant names:

• chr1-157596229-G-A
• rs10489674
• NM_031282.3:c.52+99C>T

Variant summary

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

The NM_031282.3(FCRL4):​c.52+99C>T variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.325 in 1,336,152 control chromosomes in the GnomAD database, including 71,834 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 0.31 (7312 hom., cov: 32)
  • Exomes 𝑓: 0.33 (64522 hom.)
• Consequence: FCRL4 NM_031282.3 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 0.0850

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=-0.82).
• BA1: GnomAd4 highest subpopulation (NFE) allele frequency at 95% confidence interval = 0.327 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
FCRL4	NM_031282.3	c.52+99C>T		intron_variant	Intron 2 of 11	ENST00000271532.2	NP_112572.1
FCRL4	XM_011510034.2	c.52+99C>T		intron_variant	Intron 2 of 11		XP_011508336.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
FCRL4	ENST00000271532.2	c.52+99C>T		intron_variant	Intron 2 of 11	1	NM_031282.3	ENSP00000271532.1

Frequencies

GnomAD3 genomes AF: 0.308 AC: 46813 AN: 151896 Hom.: 7295 Cov.: 32

Gnomad AFR AF: 0.287

Gnomad AMI AF: 0.383

Gnomad AMR AF: 0.312

Gnomad ASJ AF: 0.259

Gnomad EAS AF: 0.220

Gnomad SAS AF: 0.298

Gnomad FIN AF: 0.287

Gnomad MID AF: 0.389

Gnomad NFE AF: 0.331

Gnomad OTH AF: 0.338

GnomAD4 exome AF: 0.327 AC: 386972 AN: 1184138 Hom.: 64522 AF XY: 0.327 AC XY: 195956 AN XY: 600110

Gnomad4 AFR exome AF: 0.287

Gnomad4 AMR exome AF: 0.261

Gnomad4 ASJ exome AF: 0.257

Gnomad4 EAS exome AF: 0.221

Gnomad4 SAS exome AF: 0.323

Gnomad4 FIN exome AF: 0.282

Gnomad4 NFE exome AF: 0.340

Gnomad4 OTH exome AF: 0.330

GnomAD4 genome AF: 0.308 AC: 46877 AN: 152014 Hom.: 7312 Cov.: 32 AF XY: 0.306 AC XY: 22761 AN XY: 74294

Gnomad4 AFR AF: 0.288

Gnomad4 AMR AF: 0.312

Gnomad4 ASJ AF: 0.259

Gnomad4 EAS AF: 0.220

Gnomad4 SAS AF: 0.300

Gnomad4 FIN AF: 0.287

Gnomad4 NFE AF: 0.331

Gnomad4 OTH AF: 0.343

Alfa AF: 0.314 Hom.: 1210

Bravo AF: 0.310

Asia WGS AF: 0.303 AC: 1055 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.82
CADD	Benign	2.3
DANN	Benign	0.57

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: rs10489674; hg19: chr1-157566019; COSMIC: COSV54866192;