rs11574915

chr9-34710087-A-Cchr9-34710087-A-G

Variant summary

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

The NM_002989.4(CCL21):c.-21T>G variant causes a 5 prime UTR change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.126 in 1,609,770 control chromosomes in the GnomAD database, including 13,731 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 0.11 (1166 hom., cov: 32)
  • Exomes 𝑓: 0.13 (12565 hom.)
• Consequence: CCL21 NM_002989.4 5_prime_UTR
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.766

Genes affected

CCL21 (HGNC:10620): (C-C motif chemokine ligand 21) This antimicrobial gene is one of several CC cytokine genes clustered on the p-arm of chromosome 9. Cytokines are a family of secreted proteins involved in immunoregulatory and inflammatory processes. The CC cytokines are proteins characterized by two adjacent cysteines. Similar to other chemokines the protein encoded by this gene inhibits hemopoiesis and stimulates chemotaxis. This protein is chemotactic in vitro for thymocytes and activated T cells, but not for B cells, macrophages, or neutrophils. The cytokine encoded by this gene may also play a role in mediating homing of lymphocytes to secondary lymphoid organs. It is a high affinity functional ligand for chemokine receptor 7 that is expressed on T and B lymphocytes and a known receptor for another member of the cytokine family (small inducible cytokine A19). [provided by RefSeq, Sep 2014]

(HGNC:):

ACMG classification

Verdict is Benign. Variant got -12 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.87).
• BA1: GnomAd4 highest subpopulation (SAS) allele frequency at 95% confidence interval = 0.179 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
CCL21	NM_002989.4	c.-21T>G		5_prime_UTR_variant	1/4	ENST00000259607.7
PHF24	XM_047423102.1	c.133+7049A>C		intron_variant
PHF24	XM_047423103.1	c.70+7049A>C		intron_variant

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
CCL21	ENST00000259607.7	c.-21T>G		5_prime_UTR_variant	1/4	1	NM_002989.4	P1
	ENST00000664167.1	n.86+7049A>C		intron_variant, non_coding_transcript_variant
CCL21	ENST00000378792.1			upstream_gene_variant		2

Frequencies

GnomAD3 genomes AF: 0.112 AC: 17051 AN: 152114 Hom.: 1166 Cov.: 32

Gnomad AFR AF: 0.0586

Gnomad AMI AF: 0.359

Gnomad AMR AF: 0.106

Gnomad ASJ AF: 0.203

Gnomad EAS AF: 0.0484

Gnomad SAS AF: 0.188

Gnomad FIN AF: 0.148

Gnomad MID AF: 0.199

Gnomad NFE AF: 0.131

Gnomad OTH AF: 0.127

GnomAD3 exomes AF: 0.129 AC: 31411 AN: 242796 Hom.: 2217 AF XY: 0.135 AC XY: 17782 AN XY: 131244

Gnomad AFR exome AF: 0.0556

Gnomad AMR exome AF: 0.113

Gnomad ASJ exome AF: 0.208

Gnomad EAS exome AF: 0.0432

Gnomad SAS exome AF: 0.199

Gnomad FIN exome AF: 0.146

Gnomad NFE exome AF: 0.129

Gnomad OTH exome AF: 0.136

GnomAD4 exome AF: 0.128 AC: 186317 AN: 1457538 Hom.: 12565 Cov.: 32 AF XY: 0.131 AC XY: 95170 AN XY: 724880

Gnomad4 AFR exome AF: 0.0602

Gnomad4 AMR exome AF: 0.110

Gnomad4 ASJ exome AF: 0.211

Gnomad4 EAS exome AF: 0.0310

Gnomad4 SAS exome AF: 0.199

Gnomad4 FIN exome AF: 0.150

Gnomad4 NFE exome AF: 0.125

Gnomad4 OTH exome AF: 0.132

GnomAD4 genome AF: 0.112 AC: 17057 AN: 152232 Hom.: 1166 Cov.: 32 AF XY: 0.113 AC XY: 8442 AN XY: 74440

Gnomad4 AFR AF: 0.0585

Gnomad4 AMR AF: 0.106

Gnomad4 ASJ AF: 0.203

Gnomad4 EAS AF: 0.0485

Gnomad4 SAS AF: 0.189

Gnomad4 FIN AF: 0.148

Gnomad4 NFE AF: 0.131

Gnomad4 OTH AF: 0.126

Alfa AF: 0.128 Hom.: 567

Bravo AF: 0.105

Asia WGS AF: 0.121 AC: 420 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.87
Cadd	Benign	5.4
Dann	Benign	0.63

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: rs11574915; hg19: chr9-34710084; COSMIC: COSV52399169; COSMIC: COSV52399169;