rs2230320

Variant names:

• chr11-118894372-C-T
• rs2230320
• NM_001716.5:c.828C>T

Variant summary

Our verdict is Benign. The variant received -21 ACMG points: 0P and 21B. BP4_Strong BP6_Very_Strong BP7 BS1 BS2

The NM_001716.5(CXCR5):​c.828C>T​(p.His276His) variant causes a synonymous change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00167 in 1,614,202 control chromosomes in the GnomAD database, including 28 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★★).

• Frequency:
  • Genomes: 𝑓 0.0086 (13 hom., cov: 32)
  • Exomes 𝑓: 0.00095 (15 hom.)
• Consequence: CXCR5 NM_001716.5 synonymous
• Clinical Significance: Benign criteria provided, multiple submitters, no conflicts B:2
• Conservation: PhyloP100: 0.0440
• Publications: 2 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]

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

Our verdict: Benign. The variant received -21 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.63).
• BP6: Variant 11-118894372-C-T is Benign according to our data. Variant chr11-118894372-C-T is described in ClinVar as Benign. ClinVar VariationId is 784217.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars.
• BP7: Synonymous conserved (PhyloP=0.044 with no splicing effect.
• BS1: Variant frequency is greater than expected in population afr. GnomAd4 allele frequency = 0.00863 (1314/152332) while in subpopulation AFR AF = 0.0298 (1237/41568). AF 95% confidence interval is 0.0284. There are 13 homozygotes in GnomAd4. There are 601 alleles in the male GnomAd4 subpopulation. Median coverage is 32. This position passed quality control check.
• BS2: High AC in GnomAd4 at 1314 AD gene.

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_001716.5. 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
	CXCR5	NM_001716.5	MANE Select	c.828C>T	p.His276His	synonymous	Exon 2 of 2	NP_001707.1	P32302-1
	CXCR5	NM_032966.2		c.693C>T	p.His231His	synonymous	Exon 1 of 1	NP_116743.1	P32302-2

Ensembl Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	CXCR5	ENST00000292174.5	TSL:1 MANE Select	c.828C>T	p.His276His	synonymous	Exon 2 of 2	ENSP00000292174.4	P32302-1
	BCL9L	ENST00000334801.7	TSL:1	c.*4043G>A		3_prime_UTR	Exon 8 of 8	ENSP00000335320.3	Q86UU0-1

Frequencies

GnomAD3 genomes AF: 0.00859 AC: 1307 AN: 152214 Hom.: 13 Cov.: 32

Gnomad AFR AF: 0.0297

Gnomad AMI AF: 0.00

Gnomad AMR AF: 0.00288

Gnomad ASJ AF: 0.00

Gnomad EAS AF: 0.00

Gnomad SAS AF: 0.00

Gnomad FIN AF: 0.00

Gnomad MID AF: 0.00

Gnomad NFE AF: 0.000191

Gnomad OTH AF: 0.00956

GnomAD2 exomes AF: 0.00214 AC: 538 AN: 251020 AF XY: 0.00144

Gnomad AFR exome AF: 0.0292

Gnomad AMR exome AF: 0.00142

Gnomad ASJ exome AF: 0.00

Gnomad EAS exome AF: 0.00

Gnomad FIN exome AF: 0.00

Gnomad NFE exome AF: 0.0000971

Gnomad OTH exome AF: 0.000489

GnomAD4 exome AF: 0.000948 AC: 1386 AN: 1461870 Hom.: 15 Cov.: 31 AF XY: 0.000777 AC XY: 565 AN XY: 727240

African (AFR) AF: 0.0309 AC: 1035 AN: 33480

American (AMR) AF: 0.00170 AC: 76 AN: 44724

Ashkenazi Jewish (ASJ) AF: 0.00 AC: 0 AN: 26136

East Asian (EAS) AF: 0.00 AC: 0 AN: 39700

South Asian (SAS) AF: 0.0000348 AC: 3 AN: 86258

European-Finnish (FIN) AF: 0.00 AC: 0 AN: 53402

Middle Eastern (MID) AF: 0.00121 AC: 7 AN: 5768

European-Non Finnish (NFE) AF: 0.000126 AC: 140 AN: 1112006

Other (OTH) AF: 0.00207 AC: 125 AN: 60396

GnomAD4 genome AF: 0.00863 AC: 1314 AN: 152332 Hom.: 13 Cov.: 32 AF XY: 0.00807 AC XY: 601 AN XY: 74494

African (AFR) AF: 0.0298 AC: 1237 AN: 41568

American (AMR) AF: 0.00287 AC: 44 AN: 15308

Ashkenazi Jewish (ASJ) AF: 0.00 AC: 0 AN: 3472

East Asian (EAS) AF: 0.00 AC: 0 AN: 5184

South Asian (SAS) AF: 0.00 AC: 0 AN: 4832

European-Finnish (FIN) AF: 0.00 AC: 0 AN: 10622

Middle Eastern (MID) AF: 0.00 AC: 0 AN: 294

European-Non Finnish (NFE) AF: 0.000191 AC: 13 AN: 68026

Other (OTH) AF: 0.00946 AC: 20 AN: 2114

Alfa AF: 0.00388 Hom.: 4

Bravo AF: 0.00957

Asia WGS AF: 0.00260 AC: 9 AN: 3478

EpiCase AF: 0.0000545

EpiControl AF: 0.000178

ClinVar

ClinVar submissions

Significance: Benign

Revision: criteria provided, multiple submitters, no conflicts

Pathogenic	VUS	Benign	Condition
-	-	2	not provided (2)

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.63
CADD	Benign	3.1
DANN	Benign	0.85
PhyloP100		0.044
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: rs2230320; hg19: chr11-118765081;