rs2227302

Positions:

• chr9-34689698-G-A

Variant summary

Our verdict is Benign. Variant got -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

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]

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]

CCL19 (HGNC:):

ACMG classification

Verdict is Benign. Variant got -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.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
CCL19	NM_006274.3	c.*121C>T		3_prime_UTR_variant	4/4	ENST00000311925.7	NP_006265.1
PHF24	XM_047423102.1	c.48+8481G>A		intron_variant			XP_047279058.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
CCL19	ENST00000311925.7	c.*121C>T		3_prime_UTR_variant	4/4	1	NM_006274.3	ENSP00000308815.2
CCL19	ENST00000485502.1	n.355C>T		non_coding_transcript_exon_variant	2/2	2

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

Gnomad4 AFR exome AF: 0.00449

Gnomad4 AMR exome AF: 0.0996

Gnomad4 ASJ exome AF: 0.00

Gnomad4 EAS exome AF: 0.0950

Gnomad4 SAS exome AF: 0.00288

Gnomad4 FIN exome AF: 0.00871

Gnomad4 NFE exome AF: 0.000253

Gnomad4 OTH exome AF: 0.00817

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

Gnomad4 AFR AF: 0.00460

Gnomad4 AMR AF: 0.0408

Gnomad4 ASJ AF: 0.00

Gnomad4 EAS AF: 0.0833

Gnomad4 SAS AF: 0.00518

Gnomad4 FIN AF: 0.00802

Gnomad4 NFE AF: 0.000412

Gnomad4 OTH AF: 0.00993

Alfa AF: 0.00411 Hom.: 1

Bravo AF: 0.0147

Asia WGS AF: 0.0280 AC: 96 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.83
CADD	Benign	6.4
DANN	Benign	0.54

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: rs2227302; hg19: chr9-34689695;