NM_002989.4:c.-21T>G

Variant names:

• chr9-34710087-A-C
• rs11574915
• NM_002989.4:c.-21T>G

Variant summary

Our verdict is Benign. The variant received -12 ACMG points: 0P and 12B. BP4_Strong BA1

The NM_002989.4(CCL21):​c.-21T>G variant causes a 5 prime UTR premature start codon gain 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_premature_start_codon_gain
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.766
• Publications: 21 publications found

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]

ENSG00000230074 (HGNC:):

PHF24 (HGNC:29180): (PHD finger protein 24) Predicted to enable metal ion binding activity. Predicted to act upstream of or within several processes, including detection of mechanical stimulus involved in sensory perception of pain; gamma-aminobutyric acid signaling pathway; and regulation of GABAergic synaptic transmission. [provided by Alliance of Genome Resources, Apr 2022]

ACMG classification

Our verdict: Benign. The variant received -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 rank	MANE	Protein	UniProt
CCL21	NM_002989.4	c.-21T>G		5_prime_UTR_premature_start_codon_gain_variant	Exon 1 of 4	ENST00000259607.7	NP_002980.1
CCL21	NM_002989.4	c.-21T>G		5_prime_UTR_variant	Exon 1 of 4	ENST00000259607.7	NP_002980.1
PHF24	XM_047423102.1	c.133+7049A>C		intron_variant	Intron 4 of 11		XP_047279058.1
PHF24	XM_047423103.1	c.70+7049A>C		intron_variant	Intron 2 of 9		XP_047279059.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
CCL21	ENST00000259607.7	c.-21T>G		5_prime_UTR_premature_start_codon_gain_variant	Exon 1 of 4	1	NM_002989.4	ENSP00000259607.2
CCL21	ENST00000259607.7	c.-21T>G		5_prime_UTR_variant	Exon 1 of 4	1	NM_002989.4	ENSP00000259607.2

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

GnomAD2 exomes AF: 0.129 AC: 31411 AN: 242796 AF XY: 0.135

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 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

African (AFR) AF: 0.0602 AC: 2009 AN: 33396

American (AMR) AF: 0.110 AC: 4880 AN: 44202

Ashkenazi Jewish (ASJ) AF: 0.211 AC: 5481 AN: 26036

East Asian (EAS) AF: 0.0310 AC: 1226 AN: 39598

South Asian (SAS) AF: 0.199 AC: 17078 AN: 85762

European-Finnish (FIN) AF: 0.150 AC: 7963 AN: 53216

Middle Eastern (MID) AF: 0.179 AC: 1032 AN: 5750

European-Non Finnish (NFE) AF: 0.125 AC: 138711 AN: 1109340

Other (OTH) AF: 0.132 AC: 7937 AN: 60238

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

African (AFR) AF: 0.0585 AC: 2432 AN: 41548

American (AMR) AF: 0.106 AC: 1619 AN: 15298

Ashkenazi Jewish (ASJ) AF: 0.203 AC: 703 AN: 3466

East Asian (EAS) AF: 0.0485 AC: 251 AN: 5174

South Asian (SAS) AF: 0.189 AC: 911 AN: 4824

European-Finnish (FIN) AF: 0.148 AC: 1572 AN: 10600

Middle Eastern (MID) AF: 0.211 AC: 62 AN: 294

European-Non Finnish (NFE) AF: 0.131 AC: 8914 AN: 68004

Other (OTH) AF: 0.126 AC: 266 AN: 2114

Alfa AF: 0.125 Hom.: 639

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
PhyloP100		-0.77
PromoterAI		0.25	Neutral
Mutation Taster		=300/0	polymorphism (auto)

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