rs2227302

Variant names:

• chr9-34689698-G-A
• rs2227302
• NM_006274.3:c.*121C>T

Variant summary

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

The NM_006274.3(CCL19):​c.*121C>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 0.00879 in 1,161,082 control chromosomes in the GnomAD database, including 521 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 0.0092 (49 hom., cov: 31)
  • Exomes 𝑓: 0.0087 (472 hom.)
• Consequence: CCL19 NM_006274.3 3_prime_UTR
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 0.0310
• Publications: 3 publications found

Genes affected

CCL19 (HGNC:10617): (C-C motif chemokine ligand 19) 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. The cytokine encoded by this gene may play a role in normal lymphocyte recirculation and homing. It also plays an important role in trafficking of T cells in thymus, and in T cell and B cell migration to secondary lymphoid organs. It specifically binds to chemokine receptor CCR7. [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=-0.83).
• BA1: GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.0768 is higher than 0.05.

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_006274.3. You can select a different transcript below to see updated ACMG assignments.

RefSeq Transcripts

Selected	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	CCL19	NM_006274.3	MANE Select	c.*121C>T		3_prime_UTR	Exon 4 of 4	NP_006265.1

Ensembl Transcripts

Selected	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	CCL19	ENST00000311925.7	TSL:1 MANE Select	c.*121C>T		3_prime_UTR	Exon 4 of 4	ENSP00000308815.2
	CCL19	ENST00000485502.1	TSL:2	n.355C>T		non_coding_transcript_exon	Exon 2 of 2
	ENSG00000230074	ENST00000837931.1		n.222-13256G>A		intron	N/A

Frequencies

GnomAD3 genomes AF: 0.00923 AC: 1404 AN: 152130 Hom.: 49 Cov.: 31

Gnomad AFR AF: 0.00461

Gnomad AMI AF: 0.00

Gnomad AMR AF: 0.0407

Gnomad ASJ AF: 0.00

Gnomad EAS AF: 0.0831

Gnomad SAS AF: 0.00518

Gnomad FIN AF: 0.00802

Gnomad MID AF: 0.00316

Gnomad NFE AF: 0.000412

Gnomad OTH AF: 0.0100

GnomAD4 exome AF: 0.00872 AC: 8799 AN: 1008834 Hom.: 472 Cov.: 13 AF XY: 0.00774 AC XY: 3985 AN XY: 514884

African (AFR) AF: 0.00449 AC: 109 AN: 24264

American (AMR) AF: 0.0996 AC: 3936 AN: 39510

Ashkenazi Jewish (ASJ) AF: 0.00 AC: 0 AN: 19834

East Asian (EAS) AF: 0.0950 AC: 3563 AN: 37516

South Asian (SAS) AF: 0.00288 AC: 198 AN: 68676

European-Finnish (FIN) AF: 0.00871 AC: 440 AN: 50496

Middle Eastern (MID) AF: 0.000895 AC: 3 AN: 3352

European-Non Finnish (NFE) AF: 0.000253 AC: 182 AN: 720134

Other (OTH) AF: 0.00817 AC: 368 AN: 45052

GnomAD4 genome AF: 0.00923 AC: 1406 AN: 152248 Hom.: 49 Cov.: 31 AF XY: 0.0100 AC XY: 744 AN XY: 74436

African (AFR) AF: 0.00460 AC: 191 AN: 41538

American (AMR) AF: 0.0408 AC: 624 AN: 15294

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

East Asian (EAS) AF: 0.0833 AC: 431 AN: 5174

South Asian (SAS) AF: 0.00518 AC: 25 AN: 4822

European-Finnish (FIN) AF: 0.00802 AC: 85 AN: 10604

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

European-Non Finnish (NFE) AF: 0.000412 AC: 28 AN: 68024

Other (OTH) AF: 0.00993 AC: 21 AN: 2114

Alfa AF: 0.00460 Hom.: 6

Bravo AF: 0.0147

Asia WGS AF: 0.0280 AC: 96 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.83
CADD	Benign	6.4
DANN	Benign	0.54
PhyloP100		0.031
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: rs2227302; hg19: chr9-34689695;