rs630923

Variant names:

• chr11-118883644-C-A
• rs630923
• NM_001716.5:c.-298C>A

Variant summary

Our verdict is Benign. The variant received -20 ACMG points: 0P and 20B. BP4_Strong BP6_Very_Strong BA1

The NM_001716.5(CXCR5):​c.-298C>A variant causes a upstream gene change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.136 in 454,366 control chromosomes in the GnomAD database, including 5,095 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★★).

• Frequency:
  • Genomes: 𝑓 0.13 (1715 hom., cov: 31)
  • Exomes 𝑓: 0.14 (3380 hom.)
• Consequence: CXCR5 NM_001716.5 upstream_gene
• Clinical Significance: Benign criteria provided, multiple submitters, no conflicts B:2
• Conservation: PhyloP100: -0.522
• Publications: 71 publications found

Genes affected

CXCR5 (HGNC:1060): (C-X-C motif chemokine receptor 5) This gene encodes a multi-pass membrane protein that belongs to the CXC chemokine receptor family. It is expressed in mature B-cells and Burkitt's lymphoma. This cytokine receptor binds to B-lymphocyte chemoattractant (BLC), and is involved in B-cell migration into B-cell follicles of spleen and Peyer patches. Alternatively spliced transcript variants encoding different isoforms have been described for this gene. [provided by RefSeq, Aug 2011]

ACMG classification

Our verdict: Benign. The variant received -20 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.8).
• BP6: Variant 11-118883644-C-A is Benign according to our data. Variant chr11-118883644-C-A is described in ClinVar as Benign. ClinVar VariationId is 1259198.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars.
• BA1: GnomAd4 highest subpopulation (AMR) allele frequency at 95% confidence interval = 0.22 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
CXCR5	NM_001716.5	c.-298C>A		upstream_gene_variant		ENST00000292174.5	NP_001707.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
CXCR5	ENST00000292174.5	c.-298C>A		upstream_gene_variant		1	NM_001716.5	ENSP00000292174.4

Frequencies

GnomAD3 genomes AF: 0.132 AC: 20064 AN: 151904 Hom.: 1708 Cov.: 31

Gnomad AFR AF: 0.0322

Gnomad AMI AF: 0.263

Gnomad AMR AF: 0.225

Gnomad ASJ AF: 0.142

Gnomad EAS AF: 0.0599

Gnomad SAS AF: 0.105

Gnomad FIN AF: 0.243

Gnomad MID AF: 0.136

Gnomad NFE AF: 0.160

Gnomad OTH AF: 0.138

GnomAD4 exome AF: 0.139 AC: 41913 AN: 302344 Hom.: 3380 AF XY: 0.137 AC XY: 21692 AN XY: 157800

African (AFR) AF: 0.0304 AC: 309 AN: 10148

American (AMR) AF: 0.210 AC: 2889 AN: 13732

Ashkenazi Jewish (ASJ) AF: 0.129 AC: 1246 AN: 9632

East Asian (EAS) AF: 0.0452 AC: 1075 AN: 23768

South Asian (SAS) AF: 0.0997 AC: 2715 AN: 27240

European-Finnish (FIN) AF: 0.218 AC: 3920 AN: 18010

Middle Eastern (MID) AF: 0.138 AC: 173 AN: 1252

European-Non Finnish (NFE) AF: 0.150 AC: 27038 AN: 180700

Other (OTH) AF: 0.143 AC: 2548 AN: 17862

GnomAD4 genome AF: 0.132 AC: 20078 AN: 152022 Hom.: 1715 Cov.: 31 AF XY: 0.137 AC XY: 10146 AN XY: 74288

African (AFR) AF: 0.0321 AC: 1331 AN: 41476

American (AMR) AF: 0.226 AC: 3447 AN: 15266

Ashkenazi Jewish (ASJ) AF: 0.142 AC: 494 AN: 3468

East Asian (EAS) AF: 0.0605 AC: 313 AN: 5176

South Asian (SAS) AF: 0.105 AC: 508 AN: 4824

European-Finnish (FIN) AF: 0.243 AC: 2559 AN: 10534

Middle Eastern (MID) AF: 0.126 AC: 37 AN: 294

European-Non Finnish (NFE) AF: 0.160 AC: 10861 AN: 67958

Other (OTH) AF: 0.136 AC: 288 AN: 2114

Alfa AF: 0.146 Hom.: 6181

Bravo AF: 0.125

ClinVar

Significance: Benign

Submissions summary: Benign:2

Revision: criteria provided, multiple submitters, no conflicts

Submissions by phenotype

not provided Benign:2

-

Breakthrough Genomics, Breakthrough Genomics

Significance: Benign

Review Status: criteria provided, single submitter

Collection Method: not provided

- -

Feb 24, 2021

GeneDx

Significance: Benign

Review Status: criteria provided, single submitter

Collection Method: clinical testing

This variant is associated with the following publications: (PMID: 27909439) -

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.80
CADD	Benign	5.3
DANN	Benign	0.72
PhyloP100		-0.52
PromoterAI		0.017	Neutral
Mutation Taster		=100/0	polymorphism

Splicing

Find out detailed SpliceAI scores and Pangolin per-transcript scores at spliceailookup.broadinstitute.org

Other links and lift over

dbSNP: rs630923; hg19: chr11-118754353;