4-77586643-T-C

Variant names:

• chr4-77586643-T-C
• rs355689
• ENST00000286758.4:c.-42-19181T>C

Variant summary

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

The ENST00000286758.4(CXCL13):​c.-42-19181T>C variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.31 in 151,984 control chromosomes in the GnomAD database, including 8,451 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 (8451 hom., cov: 32)
• Consequence: CXCL13 ENST00000286758.4 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.874
• Publications: 6 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=-0.82).
• BA1: GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.474 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
LOC105377296	XR_007058151.1	n.1011A>G		non_coding_transcript_exon_variant	Exon 6 of 9
LOC105377296	XR_938912.3	n.1295A>G		non_coding_transcript_exon_variant	Exon 5 of 7
CXCL13	NM_006419.3	c.-42-19181T>C		intron_variant	Intron 1 of 4		NP_006410.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
CXCL13	ENST00000286758.4	c.-42-19181T>C		intron_variant	Intron 1 of 4	1		ENSP00000286758.4

Frequencies

GnomAD3 genomes AF: 0.310 AC: 47099 AN: 151866 Hom.: 8426 Cov.: 32

Gnomad AFR AF: 0.479

Gnomad AMI AF: 0.197

Gnomad AMR AF: 0.227

Gnomad ASJ AF: 0.349

Gnomad EAS AF: 0.00289

Gnomad SAS AF: 0.116

Gnomad FIN AF: 0.252

Gnomad MID AF: 0.376

Gnomad NFE AF: 0.272

Gnomad OTH AF: 0.311

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

GnomAD4 genome AF: 0.310 AC: 47171 AN: 151984 Hom.: 8451 Cov.: 32 AF XY: 0.303 AC XY: 22508 AN XY: 74304

African (AFR) AF: 0.479 AC: 19846 AN: 41408

American (AMR) AF: 0.226 AC: 3453 AN: 15274

Ashkenazi Jewish (ASJ) AF: 0.349 AC: 1209 AN: 3464

East Asian (EAS) AF: 0.00289 AC: 15 AN: 5186

South Asian (SAS) AF: 0.116 AC: 561 AN: 4822

European-Finnish (FIN) AF: 0.252 AC: 2672 AN: 10584

Middle Eastern (MID) AF: 0.387 AC: 113 AN: 292

European-Non Finnish (NFE) AF: 0.272 AC: 18473 AN: 67938

Other (OTH) AF: 0.309 AC: 650 AN: 2106

Alfa AF: 0.273 Hom.: 11391

Bravo AF: 0.327

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.82
CADD	Benign	0.087
DANN	Benign	0.42
PhyloP100		-0.87
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: rs355689; hg19: chr4-78507797;