rs11574916

Variant names:

• chr9-34709242-G-A
• rs11574916
• NM_002989.4:c.*152C>T

Variant summary

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

The NM_002989.4(CCL21):​c.*152C>T variant causes a 3 prime UTR change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00522 in 929,378 control chromosomes in the GnomAD database, including 108 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 0.017 (60 hom., cov: 32)
  • Exomes 𝑓: 0.0030 (48 hom.)
• Consequence: CCL21 NM_002989.4 3_prime_UTR
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 0.797
• Publications: 3 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]

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]

ENSG00000230074 (HGNC:):

ACMG classification

Our verdict: Benign. The variant received -12 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.8).
• BA1: GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.0512 is higher than 0.05.

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_002989.4. 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
	CCL21	NM_002989.4	MANE Select	c.*152C>T		3_prime_UTR	Exon 4 of 4	NP_002980.1

Ensembl Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	CCL21	ENST00000259607.7	TSL:1 MANE Select	c.*152C>T		3_prime_UTR	Exon 4 of 4	ENSP00000259607.2
	CCL21	ENST00000885823.1		c.*152C>T		3_prime_UTR	Exon 4 of 4	ENSP00000555882.1
	CCL21	ENST00000714163.1		c.*180C>T		3_prime_UTR	Exon 4 of 4	ENSP00000519452.1

Frequencies

GnomAD3 genomes AF: 0.0166 AC: 2523 AN: 152064 Hom.: 59 Cov.: 32

Gnomad AFR AF: 0.0530

Gnomad AMI AF: 0.00

Gnomad AMR AF: 0.00805

Gnomad ASJ AF: 0.0360

Gnomad EAS AF: 0.000193

Gnomad SAS AF: 0.000207

Gnomad FIN AF: 0.00

Gnomad MID AF: 0.00316

Gnomad NFE AF: 0.000691

Gnomad OTH AF: 0.0153

GnomAD4 exome AF: 0.00298 AC: 2315 AN: 777196 Hom.: 48 Cov.: 11 AF XY: 0.00263 AC XY: 1082 AN XY: 410976

African (AFR) AF: 0.0569 AC: 1052 AN: 18484

American (AMR) AF: 0.00443 AC: 129 AN: 29150

Ashkenazi Jewish (ASJ) AF: 0.0315 AC: 613 AN: 19464

East Asian (EAS) AF: 0.00 AC: 0 AN: 36470

South Asian (SAS) AF: 0.000169 AC: 11 AN: 65090

European-Finnish (FIN) AF: 0.00 AC: 0 AN: 50064

Middle Eastern (MID) AF: 0.00439 AC: 12 AN: 2736

European-Non Finnish (NFE) AF: 0.000492 AC: 255 AN: 518090

Other (OTH) AF: 0.00645 AC: 243 AN: 37648

GnomAD4 genome AF: 0.0167 AC: 2534 AN: 152182 Hom.: 60 Cov.: 32 AF XY: 0.0157 AC XY: 1170 AN XY: 74386

African (AFR) AF: 0.0531 AC: 2204 AN: 41510

American (AMR) AF: 0.00798 AC: 122 AN: 15294

Ashkenazi Jewish (ASJ) AF: 0.0360 AC: 125 AN: 3470

East Asian (EAS) AF: 0.000194 AC: 1 AN: 5158

South Asian (SAS) AF: 0.000415 AC: 2 AN: 4816

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

Middle Eastern (MID) AF: 0.00340 AC: 1 AN: 294

European-Non Finnish (NFE) AF: 0.000691 AC: 47 AN: 67990

Other (OTH) AF: 0.0151 AC: 32 AN: 2116

Alfa AF: 0.00837 Hom.: 18

Bravo AF: 0.0190

Asia WGS AF: 0.00260 AC: 9 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.80
CADD	Benign	8.3
DANN	Benign	0.64
PhyloP100		0.80
Mutation Taster		=100/0	polymorphism

Splicing

Name	Calibrated prediction	Score	Prediction
SpliceAI score (max)		0.030		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: rs11574916; hg19: chr9-34709239;