ENST00000496375.1:n.518+489C>T

Variant names:

• chr10-44385487-G-A
• rs17880313
• ENST00000496375.1:n.518+489C>T

Variant summary

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

The ENST00000496375.1(CXCL12):​n.518+489C>T variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0847 in 152,282 control chromosomes in the GnomAD database, including 759 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 0.085 (759 hom., cov: 33)
• Consequence: CXCL12 ENST00000496375.1 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.984
• Publications: 3 publications found

Genes affected

CXCL12 (HGNC:10672): (C-X-C motif chemokine ligand 12) This antimicrobial gene encodes a stromal cell-derived alpha chemokine member of the intercrine family. The encoded protein functions as the ligand for the G-protein coupled receptor, chemokine (C-X-C motif) receptor 4, and plays a role in many diverse cellular functions, including embryogenesis, immune surveillance, inflammation response, tissue homeostasis, and tumor growth and metastasis. Mutations in this gene are associated with resistance to human immunodeficiency virus type 1 infections. Multiple transcript variants encoding different isoforms have been found for this gene. [provided by RefSeq, Sep 2014]

ENSG00000303087 (HGNC:):

ACMG classification

Our verdict: Benign. The variant received -12 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.85).
• BA1: GnomAd4 highest subpopulation (NFE) allele frequency at 95% confidence interval = 0.131 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
CXCL12	ENST00000496375.1	n.518+489C>T		intron_variant	Intron 1 of 2	5
ENSG00000303087	ENST00000791650.1	n.51+1311G>A		intron_variant	Intron 1 of 4

Frequencies

GnomAD3 genomes AF: 0.0848 AC: 12908 AN: 152164 Hom.: 759 Cov.: 33

Gnomad AFR AF: 0.0229

Gnomad AMI AF: 0.136

Gnomad AMR AF: 0.0716

Gnomad ASJ AF: 0.0680

Gnomad EAS AF: 0.000579

Gnomad SAS AF: 0.0178

Gnomad FIN AF: 0.111

Gnomad MID AF: 0.0443

Gnomad NFE AF: 0.133

Gnomad OTH AF: 0.0900

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

GnomAD4 genome AF: 0.0847 AC: 12905 AN: 152282 Hom.: 759 Cov.: 33 AF XY: 0.0824 AC XY: 6131 AN XY: 74450

African (AFR) AF: 0.0228 AC: 948 AN: 41592

American (AMR) AF: 0.0715 AC: 1094 AN: 15302

Ashkenazi Jewish (ASJ) AF: 0.0680 AC: 236 AN: 3470

East Asian (EAS) AF: 0.000581 AC: 3 AN: 5166

South Asian (SAS) AF: 0.0180 AC: 87 AN: 4828

European-Finnish (FIN) AF: 0.111 AC: 1173 AN: 10614

Middle Eastern (MID) AF: 0.0476 AC: 14 AN: 294

European-Non Finnish (NFE) AF: 0.133 AC: 9038 AN: 67992

Other (OTH) AF: 0.0890 AC: 188 AN: 2112

Alfa AF: 0.0969 Hom.: 168

Bravo AF: 0.0806

Asia WGS AF: 0.0130 AC: 46 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.85
CADD	Benign	5.6
DANN	Benign	0.84
PhyloP100		-0.98
PromoterAI		0.26	Neutral

Splicing

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

Other links and lift over

dbSNP: rs17880313; hg19: chr10-44880935;