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. The variant received -12 ACMG points: 0P and 12B. BP4_Strong BA1

The ENST00000664167.1(ENSG00000230074):​n.86+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: ENSG00000230074 ENST00000664167.1 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.223
• Publications: 95 publications found

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]

ENSG00000230074 (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

Our verdict: Benign. The variant received -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.

Variant Effect in Transcripts

ACMG analysis was done for transcript: ENST00000664167.1. You can select a different transcript below to see updated ACMG assignments.

RefSeq Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	CCL21	NM_002989.4	MANE Select	c.-197C>T		upstream_gene	N/A	NP_002980.1	O00585

Ensembl Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	ENSG00000230074	ENST00000664167.1		n.86+7225G>A		intron	N/A
	ENSG00000230074	ENST00000837930.1		n.174+7225G>A		intron	N/A
	ENSG00000230074	ENST00000837931.1		n.306+7225G>A		intron	N/A

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

African (AFR) AF: 0.587 AC: 7210 AN: 12284

American (AMR) AF: 0.715 AC: 13201 AN: 18456

Ashkenazi Jewish (ASJ) AF: 0.724 AC: 9695 AN: 13384

East Asian (EAS) AF: 0.948 AC: 28702 AN: 30268

South Asian (SAS) AF: 0.655 AC: 29524 AN: 45062

European-Finnish (FIN) AF: 0.722 AC: 21742 AN: 30106

Middle Eastern (MID) AF: 0.712 AC: 1351 AN: 1898

European-Non Finnish (NFE) AF: 0.663 AC: 174885 AN: 263768

Other (OTH) AF: 0.688 AC: 17436 AN: 25326

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

African (AFR) AF: 0.589 AC: 24392 AN: 41438

American (AMR) AF: 0.708 AC: 10815 AN: 15284

Ashkenazi Jewish (ASJ) AF: 0.728 AC: 2526 AN: 3468

East Asian (EAS) AF: 0.930 AC: 4806 AN: 5168

South Asian (SAS) AF: 0.661 AC: 3187 AN: 4818

European-Finnish (FIN) AF: 0.739 AC: 7823 AN: 10582

Middle Eastern (MID) AF: 0.704 AC: 207 AN: 294

European-Non Finnish (NFE) AF: 0.667 AC: 45372 AN: 67974

Other (OTH) AF: 0.700 AC: 1476 AN: 2110

Alfa AF: 0.667 Hom.: 94835

Bravo AF: 0.661

Asia WGS AF: 0.778 AC: 2709 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.99
CADD	Benign	0.96
DANN	Benign	0.22
PhyloP100		-0.22
PromoterAI		-0.034	Neutral
Mutation Taster		=100/0	polymorphism

Splicing

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

Other links and lift over

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