rs767463762

Variant names:

• chr4-77605920-C-G
• rs767463762
• NM_001371558.1:c.55C>G

Your query was ambiguous. Multiple possible variants found:

• chr4-77605920-C-G
• chr4-77605920-C-T

Variant summary

Our verdict is Uncertain significance. The variant received 0 ACMG points: 2P and 2B. PM2 BP4_Moderate

The NM_001371558.1(CXCL13):​c.55C>G​(p.Pro19Ala) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00000138 in 1,448,856 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a benign outcome for this variant. 16/22 in silico tools predict a benign outcome for this variant. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar. Another variant affecting the same amino acid position, but resulting in a different missense (i.e. P19S) has been classified as Uncertain significance.

• Frequency:
  • Genomes: not found (cov: 32)
  • Exomes 𝑓: 0.0000014 (0 hom.)
• Consequence: CXCL13 NM_001371558.1 missense
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 0.779
• Publications: 0 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]

ACMG classification

Our verdict: Uncertain_significance. The variant received 0 ACMG points.

• PM2: Very rare variant in population databases, with high coverage
• BP4: Computational evidence support a benign effect (MetaRNN=0.21133134).

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_001371558.1. You can select a different transcript below to see updated ACMG assignments.

RefSeq Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	CXCL13	NM_001371558.1	MANE Select	c.55C>G	p.Pro19Ala	missense	Exon 1 of 4	NP_001358487.1	O43927
	CXCL13	NM_006419.3		c.55C>G	p.Pro19Ala	missense	Exon 2 of 5	NP_006410.1	O43927

Ensembl Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	CXCL13	ENST00000682537.1	MANE Select	c.55C>G	p.Pro19Ala	missense	Exon 1 of 4	ENSP00000507688.1	O43927
	CXCL13	ENST00000286758.4	TSL:1	c.55C>G	p.Pro19Ala	missense	Exon 2 of 5	ENSP00000286758.4	O43927
	CXCL13	ENST00000506590.1	TSL:2	n.89C>G		non_coding_transcript_exon	Exon 1 of 3

Frequencies

GnomAD3 genomes Cov.: 32

GnomAD4 exome AF: 0.00000138 AC: 2 AN: 1448856 Hom.: 0 Cov.: 27 AF XY: 0.00000139 AC XY: 1 AN XY: 720464

African (AFR) AF: 0.00 AC: 0 AN: 33300

American (AMR) AF: 0.00 AC: 0 AN: 44216

Ashkenazi Jewish (ASJ) AF: 0.00 AC: 0 AN: 25974

East Asian (EAS) AF: 0.00 AC: 0 AN: 39544

South Asian (SAS) AF: 0.00 AC: 0 AN: 84116

European-Finnish (FIN) AF: 0.00 AC: 0 AN: 53242

Middle Eastern (MID) AF: 0.00 AC: 0 AN: 5740

European-Non Finnish (NFE) AF: 0.00000181 AC: 2 AN: 1102856

Other (OTH) AF: 0.00 AC: 0 AN: 59868

GnomAD4 genome Cov.: 32

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
AlphaMissense	Benign	0.13
BayesDel_addAF	Benign	-0.29	T
BayesDel_noAF	Benign	-0.65
CADD	Benign	17
DANN	Benign	0.50
DEOGEN2	Benign	0.21	T
Eigen	Benign	-0.39
Eigen_PC	Benign	-0.47
FATHMM_MKL	Benign	0.050	N
LIST_S2	Benign	0.49	T
M_CAP	Benign	0.0048	T
MetaRNN	Benign	0.21	T
MetaSVM	Benign	-1.0	T
MutationAssessor	Benign	1.1	L
PhyloP100		0.78
PrimateAI	Benign	0.32	T
PROVEAN	Benign	-1.9	N
REVEL	Benign	0.075
Sift	Benign	0.48	T
Sift4G	Benign	0.36	T
Polyphen		0.94	P
Vest4		0.33
MutPred		0.48		Gain of catalytic residue at P19 (P = 0.0555)
MVP		0.30
MPC		0.67
ClinPred		0.78	D
GERP RS		2.1
PromoterAI		-0.053	Neutral
Varity_R		0.032
gMVP		0.40
Mutation Taster		=89/11	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: rs767463762; hg19: chr4-78527074;