ENST00000664167.1:n.86+7303G>A

Variant names:

• chr9-34710341-G-A
• rs11574914
• ENST00000664167.1:n.86+7303G>A

Variant summary

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

The ENST00000664167.1(ENSG00000230074):​n.86+7303G>A variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.242 in 152,008 control chromosomes in the GnomAD database, including 5,343 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 0.24 (5343 hom., cov: 32)
• Consequence: ENSG00000230074 ENST00000664167.1 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 1.87
• Publications: 43 publications found

Genes affected

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]

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=-0.81).
• BA1: GnomAd4 highest subpopulation (SAS) allele frequency at 95% confidence interval = 0.328 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
PHF24	XM_047423102.1	c.133+7303G>A		intron_variant	Intron 4 of 11		XP_047279058.1
PHF24	XM_047423103.1	c.70+7303G>A		intron_variant	Intron 2 of 9		XP_047279059.1
CCL21	NM_002989.4	c.-275C>T		upstream_gene_variant		ENST00000259607.7	NP_002980.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
CCL21	ENST00000259607.7	c.-275C>T		upstream_gene_variant		1	NM_002989.4	ENSP00000259607.2

Frequencies

GnomAD3 genomes AF: 0.242 AC: 36761 AN: 151890 Hom.: 5343 Cov.: 32

Gnomad AFR AF: 0.0957

Gnomad AMI AF: 0.321

Gnomad AMR AF: 0.255

Gnomad ASJ AF: 0.228

Gnomad EAS AF: 0.0693

Gnomad SAS AF: 0.338

Gnomad FIN AF: 0.262

Gnomad MID AF: 0.288

Gnomad NFE AF: 0.331

Gnomad OTH AF: 0.232

We have no GnomAD4 exomes data on this position. Probably position not covered by the project.

GnomAD4 genome AF: 0.242 AC: 36777 AN: 152008 Hom.: 5343 Cov.: 32 AF XY: 0.240 AC XY: 17796 AN XY: 74270

African (AFR) AF: 0.0956 AC: 3966 AN: 41468

American (AMR) AF: 0.255 AC: 3893 AN: 15260

Ashkenazi Jewish (ASJ) AF: 0.228 AC: 789 AN: 3468

East Asian (EAS) AF: 0.0699 AC: 362 AN: 5180

South Asian (SAS) AF: 0.339 AC: 1637 AN: 4826

European-Finnish (FIN) AF: 0.262 AC: 2751 AN: 10518

Middle Eastern (MID) AF: 0.282 AC: 83 AN: 294

European-Non Finnish (NFE) AF: 0.331 AC: 22517 AN: 67972

Other (OTH) AF: 0.230 AC: 486 AN: 2110

Alfa AF: 0.297 Hom.: 22960

Bravo AF: 0.233

Asia WGS AF: 0.196 AC: 680 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.81
CADD	Benign	11
DANN	Benign	0.57
PhyloP100		1.9
PromoterAI		-0.062	Neutral

Splicing

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

Other links and lift over

dbSNP: rs11574914; hg19: chr9-34710338;