ENST00000286758.4:c.-42-19181T>A

Variant names:

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

Variant summary

Our verdict is Benign. The variant received -12 ACMG points: 0P and 12B. BP4_Strong BS1 BS2

The ENST00000286758.4(CXCL13):​c.-42-19181T>A variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0155 in 152,028 control chromosomes in the GnomAD database, including 60 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 0.016 (60 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=-0.8).
• BS1: Variant frequency is greater than expected in population afr. GnomAd4 allele frequency = 0.0155 (2364/152028) while in subpopulation AFR AF = 0.0518 (2146/41428). AF 95% confidence interval is 0.05. There are 60 homozygotes in GnomAd4. There are 1119 alleles in the male GnomAd4 subpopulation. Median coverage is 32. This position passed quality control check.
• BS2: High Homozygotes in GnomAd4 at 60 AR gene

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
LOC105377296	XR_007058151.1	n.1011A>T		non_coding_transcript_exon_variant	Exon 6 of 9
LOC105377296	XR_938912.3	n.1295A>T		non_coding_transcript_exon_variant	Exon 5 of 7
CXCL13	NM_006419.3	c.-42-19181T>A		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>A		intron_variant	Intron 1 of 4	1		ENSP00000286758.4

Frequencies

GnomAD3 genomes AF: 0.0155 AC: 2358 AN: 151910 Hom.: 59 Cov.: 32

Gnomad AFR AF: 0.0518

Gnomad AMI AF: 0.00

Gnomad AMR AF: 0.00760

Gnomad ASJ AF: 0.0150

Gnomad EAS AF: 0.00

Gnomad SAS AF: 0.000414

Gnomad FIN AF: 0.00

Gnomad MID AF: 0.00318

Gnomad NFE AF: 0.000441

Gnomad OTH AF: 0.00815

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

GnomAD4 genome AF: 0.0155 AC: 2364 AN: 152028 Hom.: 60 Cov.: 32 AF XY: 0.0151 AC XY: 1119 AN XY: 74330

African (AFR) AF: 0.0518 AC: 2146 AN: 41428

American (AMR) AF: 0.00759 AC: 116 AN: 15280

Ashkenazi Jewish (ASJ) AF: 0.0150 AC: 52 AN: 3464

East Asian (EAS) AF: 0.00 AC: 0 AN: 5186

South Asian (SAS) AF: 0.000415 AC: 2 AN: 4822

European-Finnish (FIN) AF: 0.00 AC: 0 AN: 10586

Middle Eastern (MID) AF: 0.00342 AC: 1 AN: 292

European-Non Finnish (NFE) AF: 0.000441 AC: 30 AN: 67952

Other (OTH) AF: 0.00806 AC: 17 AN: 2108

Alfa AF: 0.00 Hom.: 11391

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.80
CADD	Benign	0.071
DANN	Benign	0.48
PhyloP100		-0.87
Mutation Taster		=100/0	polymorphism

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;