chr11-118894979-C-G

Position:

• chr11-118894979-C-G

Variant summary

Our verdict is Benign. Variant got -12 ACMG points: 0P and 12B. BP4_Strong BA1

The NM_001716.5(CXCR5):​c.*316C>G variant causes a 3 prime UTR change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.212 in 300,020 control chromosomes in the GnomAD database, including 8,263 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 0.20 (4160 hom., cov: 32)
  • Exomes 𝑓: 0.22 (4103 hom.)
• Consequence: CXCR5 NM_001716.5 3_prime_UTR
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 0.0740

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]

BCL9L (HGNC:23688): (BCL9 like) Enables beta-catenin binding activity. Involved in several processes, including negative regulation of transforming growth factor beta receptor signaling pathway; positive regulation of epithelial to mesenchymal transition; and positive regulation of transcription by RNA polymerase II. Located in nucleolus and nucleoplasm. Part of beta-catenin-TCF complex. [provided by Alliance of Genome Resources, Apr 2022]

ACMG classification

Verdict is Benign. Variant got -12 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.85).
• BA1: GnomAd4 highest subpopulation (AMR) allele frequency at 95% confidence interval = 0.365 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
CXCR5	NM_001716.5	c.*316C>G		3_prime_UTR_variant	2/2	ENST00000292174.5	NP_001707.1
CXCR5	NM_032966.2	c.*316C>G		3_prime_UTR_variant	1/1		NP_116743.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
CXCR5	ENST00000292174.5	c.*316C>G		3_prime_UTR_variant	2/2	1	NM_001716.5	ENSP00000292174	P1
BCL9L	ENST00000334801.7	c.*3436G>C		3_prime_UTR_variant	8/8	1		ENSP00000335320	P4

Frequencies

GnomAD3 genomes AF: 0.205 AC: 31109 AN: 152022 Hom.: 4147 Cov.: 32

Gnomad AFR AF: 0.0622

Gnomad AMI AF: 0.255

Gnomad AMR AF: 0.372

Gnomad ASJ AF: 0.205

Gnomad EAS AF: 0.106

Gnomad SAS AF: 0.144

Gnomad FIN AF: 0.259

Gnomad MID AF: 0.165

Gnomad NFE AF: 0.257

Gnomad OTH AF: 0.211

GnomAD4 exome AF: 0.221 AC: 32618 AN: 147880 Hom.: 4103 Cov.: 0 AF XY: 0.221 AC XY: 16344 AN XY: 73940

Gnomad4 AFR exome AF: 0.0627

Gnomad4 AMR exome AF: 0.382

Gnomad4 ASJ exome AF: 0.194

Gnomad4 EAS exome AF: 0.0541

Gnomad4 SAS exome AF: 0.133

Gnomad4 FIN exome AF: 0.250

Gnomad4 NFE exome AF: 0.238

Gnomad4 OTH exome AF: 0.225

GnomAD4 genome AF: 0.205 AC: 31135 AN: 152140 Hom.: 4160 Cov.: 32 AF XY: 0.207 AC XY: 15386 AN XY: 74386

Gnomad4 AFR AF: 0.0622

Gnomad4 AMR AF: 0.373

Gnomad4 ASJ AF: 0.205

Gnomad4 EAS AF: 0.106

Gnomad4 SAS AF: 0.144

Gnomad4 FIN AF: 0.259

Gnomad4 NFE AF: 0.256

Gnomad4 OTH AF: 0.209

Alfa AF: 0.229 Hom.: 661

Bravo AF: 0.208

Asia WGS AF: 0.115 AC: 400 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.85
CADD	Benign	3.2
DANN	Benign	0.54

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

Publications

LitVar

Other links and lift over

dbSNP: rs676925; hg19: chr11-118765688; COSMIC: COSV52690465; COSMIC: COSV52690465;