4-77584424-T-C

Variant names:

• chr4-77584424-T-C
• rs355687
• ENST00000286758.4:c.-42-21400T>C

Variant summary

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

The ENST00000286758.4(CXCL13):​c.-42-21400T>C variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.273 in 152,044 control chromosomes in the GnomAD database, including 5,783 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 0.27 (5783 hom., cov: 32)
• Consequence: CXCL13 ENST00000286758.4 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -2.47
• Publications: 12 publications found

Genes affected

CXCL13 (HGNC:10639): (C-X-C motif chemokine ligand 13) B lymphocyte chemoattractant, independently cloned and named Angie, is an antimicrobial peptide and CXC chemokine strongly expressed in the follicles of the spleen, lymph nodes, and Peyer's patches. It preferentially promotes the migration of B lymphocytes (compared to T cells and macrophages), apparently by stimulating calcium influx into, and chemotaxis of, cells expressing Burkitt's lymphoma receptor 1 (BLR-1). It may therefore function in the homing of B lymphocytes to follicles. [provided by RefSeq, Oct 2014]

LOC105377296 (HGNC:):

ACMG classification

Our verdict: Benign. The variant received -12 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.95).
• BA1: GnomAd4 highest subpopulation (SAS) allele frequency at 95% confidence interval = 0.341 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
CXCL13	NM_006419.3	c.-42-21400T>C		intron_variant	Intron 1 of 4		NP_006410.1
LOC105377296	XR_007058151.1	n.1303+523A>G		intron_variant	Intron 7 of 8
LOC105377296	XR_938912.3	n.1347-791A>G		intron_variant	Intron 5 of 6

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
CXCL13	ENST00000286758.4	c.-42-21400T>C		intron_variant	Intron 1 of 4	1		ENSP00000286758.4

Frequencies

GnomAD3 genomes AF: 0.273 AC: 41408 AN: 151926 Hom.: 5782 Cov.: 32

Gnomad AFR AF: 0.309

Gnomad AMI AF: 0.195

Gnomad AMR AF: 0.231

Gnomad ASJ AF: 0.248

Gnomad EAS AF: 0.329

Gnomad SAS AF: 0.356

Gnomad FIN AF: 0.321

Gnomad MID AF: 0.326

Gnomad NFE AF: 0.245

Gnomad OTH AF: 0.261

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

GnomAD4 genome AF: 0.273 AC: 41434 AN: 152044 Hom.: 5783 Cov.: 32 AF XY: 0.278 AC XY: 20653 AN XY: 74340

African (AFR) AF: 0.309 AC: 12798 AN: 41444

American (AMR) AF: 0.231 AC: 3528 AN: 15300

Ashkenazi Jewish (ASJ) AF: 0.248 AC: 858 AN: 3462

East Asian (EAS) AF: 0.329 AC: 1704 AN: 5180

South Asian (SAS) AF: 0.355 AC: 1714 AN: 4824

European-Finnish (FIN) AF: 0.321 AC: 3389 AN: 10562

Middle Eastern (MID) AF: 0.320 AC: 94 AN: 294

European-Non Finnish (NFE) AF: 0.245 AC: 16620 AN: 67956

Other (OTH) AF: 0.261 AC: 552 AN: 2112

Alfa AF: 0.252 Hom.: 18631

Bravo AF: 0.266

Asia WGS AF: 0.347 AC: 1208 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.95
CADD	Benign	1.4
DANN	Benign	0.55
PhyloP100		-2.5
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: rs355687; hg19: chr4-78505578;