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:):

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	P2
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;