11-118893589-C-G

Variant summary

Our verdict is Benign. Variant got -14 ACMG points: 0P and 14B. BP4_Strong BP6_Moderate BA1

The NM_001716.5(CXCR5):c.52-7C>G variant causes a splice region, splice polypyrimidine tract, intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00392 in 1,568,718 control chromosomes in the GnomAD database, including 195 homozygotes. In-silico tool predicts a benign outcome for this variant. 3/3 splice prediction tools predict no significant impact on normal splicing. Variant has been reported in ClinVar as Benign (★).

• Frequency:
  • Genomes: 𝑓 0.021 (112 hom., cov: 32)
  • Exomes 𝑓: 0.0021 (83 hom.)
• Consequence: CXCR5 NM_001716.5 splice_region, splice_polypyrimidine_tract, intron
• Scores: Splicing: ADA: 0.03682
• Clinical Significance: Benign criteria provided, single submitter B:1
• Conservation: PhyloP100: 0.364

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

Verdict is Benign. Variant got -14 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.64).
• BP6: Variant 11-118893589-C-G is Benign according to our data. Variant chr11-118893589-C-G is described in ClinVar as [Benign]. Clinvar id is 789043.Status of the report is criteria_provided_single_submitter, 1 stars.
• BA1: GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.0705 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
CXCR5	NM_001716.5	c.52-7C>G		splice_region_variant, splice_polypyrimidine_tract_variant, intron_variant		ENST00000292174.5
CXCR5	NM_032966.2	c.-91C>G		5_prime_UTR_variant	1/1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
CXCR5	ENST00000292174.5	c.52-7C>G		splice_region_variant, splice_polypyrimidine_tract_variant, intron_variant		1	NM_001716.5	P1

Frequencies

GnomAD3 genomes AF: 0.0211 AC: 3211 AN: 152196 Hom.: 112 Cov.: 32

Gnomad AFR AF: 0.0724

Gnomad AMI AF: 0.00

Gnomad AMR AF: 0.0107

Gnomad ASJ AF: 0.00

Gnomad EAS AF: 0.00

Gnomad SAS AF: 0.000414

Gnomad FIN AF: 0.00

Gnomad MID AF: 0.00

Gnomad NFE AF: 0.000220

Gnomad OTH AF: 0.0139

GnomAD3 exomes AF: 0.00584 AC: 1316 AN: 225514 Hom.: 41 AF XY: 0.00422 AC XY: 511 AN XY: 121188

Gnomad AFR exome AF: 0.0725

Gnomad AMR exome AF: 0.00400

Gnomad ASJ exome AF: 0.00

Gnomad EAS exome AF: 0.0000560

Gnomad SAS exome AF: 0.000156

Gnomad FIN exome AF: 0.00

Gnomad NFE exome AF: 0.000165

Gnomad OTH exome AF: 0.00207

GnomAD4 exome AF: 0.00207 AC: 2927 AN: 1416404 Hom.: 83 Cov.: 31 AF XY: 0.00173 AC XY: 1210 AN XY: 698446

Gnomad4 AFR exome AF: 0.0706

Gnomad4 AMR exome AF: 0.00490

Gnomad4 ASJ exome AF: 0.00

Gnomad4 EAS exome AF: 0.0000256

Gnomad4 SAS exome AF: 0.000210

Gnomad4 FIN exome AF: 0.00

Gnomad4 NFE exome AF: 0.000103

Gnomad4 OTH exome AF: 0.00508

GnomAD4 genome AF: 0.0212 AC: 3230 AN: 152314 Hom.: 112 Cov.: 32 AF XY: 0.0208 AC XY: 1547 AN XY: 74486

Gnomad4 AFR AF: 0.0727

Gnomad4 AMR AF: 0.0107

Gnomad4 ASJ AF: 0.00

Gnomad4 EAS AF: 0.00

Gnomad4 SAS AF: 0.000207

Gnomad4 FIN AF: 0.00

Gnomad4 NFE AF: 0.000221

Gnomad4 OTH AF: 0.0137

Alfa AF: 0.000902 Hom.: 1

Bravo AF: 0.0244

Asia WGS AF: 0.00404 AC: 14 AN: 3478

ClinVar

Significance: Benign

Submissions summary: Benign:1

Revision: criteria provided, single submitter

Submissions by phenotype

not provided Benign:1

Benign, criteria provided, single submitter

clinical testing

Invitae

Jun 29, 2018

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Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.64
Cadd	Benign	2.2
Dann	Benign	0.85

Splicing

Name	Calibrated prediction	Score	Prediction
dbscSNV1_ADA	Benign	0.037
dbscSNV1_RF	Benign	0.17
SpliceAI score (max)		0.11		Details are displayed if max score is > 0.2

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

Publications

LitVar

Other links and lift over

dbSNP: rs11574669; hg19: chr11-118764298;