rs2812378

Variant names:

• chr9-34710263-G-A
• rs2812378
• XM_047423102.1:c.133+7225G>A

Your query was ambiguous. Multiple possible variants found:

• chr9-34710263-G-A
• chr9-34710263-G-C
• chr9-34710263-G-T

Variant summary

Our verdict is Benign. Variant got -12 ACMG points: 0P and 12B. BP4_Strong BA1

The XM_047423102.1(PHF24):​c.133+7225G>A variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.683 in 592,598 control chromosomes in the GnomAD database, including 140,475 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 0.67 (34177 hom., cov: 31)
  • Exomes 𝑓: 0.69 (106298 hom.)
• Consequence: PHF24 XM_047423102.1 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.223

Genes affected

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]

ENSG00000288583 (HGNC:):

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]

ACMG classification

Verdict is Benign. Variant got -12 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.99).
• BA1: GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.908 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
PHF24	XM_047423102.1	c.133+7225G>A		intron_variant	Intron 4 of 11		XP_047279058.1
PHF24	XM_047423103.1	c.70+7225G>A		intron_variant	Intron 2 of 9		XP_047279059.1
CCL21	NM_002989.4	c.-197C>T		upstream_gene_variant		ENST00000259607.7	NP_002980.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
ENSG00000288583	ENST00000664167.1	n.86+7225G>A		intron_variant	Intron 1 of 1
CCL21	ENST00000259607.7	c.-197C>T		upstream_gene_variant		1	NM_002989.4	ENSP00000259607.2
CCL21	ENST00000378792.1	c.-197C>T		upstream_gene_variant		2		ENSP00000368069.1

Frequencies

GnomAD3 genomes AF: 0.666 AC: 101177 AN: 151924 Hom.: 34168 Cov.: 31

Gnomad AFR AF: 0.589

Gnomad AMI AF: 0.680

Gnomad AMR AF: 0.708

Gnomad ASJ AF: 0.728

Gnomad EAS AF: 0.931

Gnomad SAS AF: 0.663

Gnomad FIN AF: 0.739

Gnomad MID AF: 0.702

Gnomad NFE AF: 0.667

Gnomad OTH AF: 0.697

GnomAD4 exome AF: 0.689 AC: 303746 AN: 440552 Hom.: 106298 AF XY: 0.689 AC XY: 159386 AN XY: 231340

Gnomad4 AFR exome AF: 0.587

Gnomad4 AMR exome AF: 0.715

Gnomad4 ASJ exome AF: 0.724

Gnomad4 EAS exome AF: 0.948

Gnomad4 SAS exome AF: 0.655

Gnomad4 FIN exome AF: 0.722

Gnomad4 NFE exome AF: 0.663

Gnomad4 OTH exome AF: 0.688

GnomAD4 genome AF: 0.666 AC: 101223 AN: 152046 Hom.: 34177 Cov.: 31 AF XY: 0.671 AC XY: 49885 AN XY: 74308

Gnomad4 AFR AF: 0.589

Gnomad4 AMR AF: 0.708

Gnomad4 ASJ AF: 0.728

Gnomad4 EAS AF: 0.930

Gnomad4 SAS AF: 0.661

Gnomad4 FIN AF: 0.739

Gnomad4 NFE AF: 0.667

Gnomad4 OTH AF: 0.700

Alfa AF: 0.670 Hom.: 34156

Bravo AF: 0.661

Asia WGS AF: 0.778 AC: 2709 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.99
CADD	Benign	0.96
DANN	Benign	0.22

Splicing

Find out detailed SpliceAI scores and Pangolin per-transcript scores at spliceailookup.broadinstitute.org

Publications

LitVar

Other links and lift over

dbSNP: rs2812378; hg19: chr9-34710260; COSMIC: COSV52398692;