Variant rs11574915 details in Genebe, Genetics Data Aggregator

Variant summary

Our verdict is Benign. Variant got -12 ACMG points: 0P and 12B. BP4_StrongBA1

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

Scores

Clinical Significance

Not reported in ClinVar

Conservation

PhyloP100: -0.766

Variant links:

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]

CCL21 links:

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]

PHF24 links:

ENSG00000288583 (HGNC:):

ENSG00000288583 links:

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ACMG classification

Classification made for transcript

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	Effect	#exon/exons	MANE	Protein	UniProt
CCL21	NM_002989.4 linkuse as main transcript	c.-21T>G	5_prime_UTR_premature_start_codon_gain_variant	1/4	ENST00000259607.7	NP_002980.1	O00585
CCL21	NM_002989.4 linkuse as main transcript	c.-21T>G	5_prime_UTR_variant	1/4	ENST00000259607.7	NP_002980.1	O00585
PHF24	XM_047423102.1 linkuse as main transcript	c.133+7049A>C	intron_variant			XP_047279058.1
PHF24	XM_047423103.1 linkuse as main transcript	c.70+7049A>C	intron_variant			XP_047279059.1

Ensembl

Gene	Transcript	HGVSc	Effect	#exon/exons	TSL	MANE	Protein	UniProt
CCL21	ENST00000259607.7 linkuse as main transcript	c.-21T>G	5_prime_UTR_premature_start_codon_gain_variant	1/4	1	NM_002989.4	ENSP00000259607.2	O00585
CCL21	ENST00000259607.7 linkuse as main transcript	c.-21T>G	5_prime_UTR_variant	1/4	1	NM_002989.4	ENSP00000259607.2	O00585
ENSG00000288583	ENST00000664167.1 linkuse as main transcript	n.86+7049A>C	intron_variant
CCL21	ENST00000378792.1 linkuse as main transcript	c.-21T>G	upstream_gene_variant		2		ENSP00000368069.1	Q5VZ73

Frequencies

GnomAD3 genomes

AF:

0.112

AC:

17051

AN:

152114

Hom.:

1166

Cov.:

show subpopulations

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

show subpopulations

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.:

AF XY:

0.131

AC XY:

95170

AN XY:

724880

show subpopulations

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.:

AF XY:

0.113

AC XY:

8442

AN XY:

74440

show subpopulations

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

Below is the list of publications found by LitVar. It may be empty.

Variant summary

Frequency

Consequence

Scores

Clinical Significance

Conservation

ACMG classification

Transcripts

RefSeq

Ensembl

Frequencies

ClinVar

Computational scores

Splicing

Publications

LitVar

Other links and lift over