ENST00000496375.1:n.304T>C

Variant names:

• chr10-44386190-A-G
• rs2839685
• ENST00000496375.1:n.304T>C

Variant summary

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

The ENST00000496375.1(CXCL12):​n.304T>C variant causes a non coding transcript exon change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.828 in 152,104 control chromosomes in the GnomAD database, including 52,574 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 0.83 (52503 hom., cov: 30)
  • Exomes 𝑓: 0.84 (71 hom.)
• Consequence: CXCL12 ENST00000496375.1 non_coding_transcript_exon
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -1.39
• Publications: 13 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=-0.89).
• BA1: GnomAd4 highest subpopulation (AMR) allele frequency at 95% confidence interval = 0.897 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.304T>C		non_coding_transcript_exon_variant	Exon 1 of 3	5
ENSG00000303087	ENST00000791650.1	n.51+2014A>G		intron_variant	Intron 1 of 4

Frequencies

GnomAD3 genomes AF: 0.828 AC: 125734 AN: 151790 Hom.: 52462 Cov.: 30

Gnomad AFR AF: 0.712

Gnomad AMI AF: 0.844

Gnomad AMR AF: 0.909

Gnomad ASJ AF: 0.849

Gnomad EAS AF: 0.849

Gnomad SAS AF: 0.867

Gnomad FIN AF: 0.929

Gnomad MID AF: 0.848

Gnomad NFE AF: 0.858

Gnomad OTH AF: 0.861

GnomAD4 exome AF: 0.842 AC: 165 AN: 196 Hom.: 71 Cov.: 0 AF XY: 0.843 AC XY: 113 AN XY: 134

African (AFR) AF: 0.750 AC: 3 AN: 4

American (AMR) AF: 1.00 AC: 2 AN: 2

Ashkenazi Jewish (ASJ) AC: 0 AN: 0

East Asian (EAS) AF: 0.500 AC: 3 AN: 6

South Asian (SAS) AF: 1.00 AC: 2 AN: 2

European-Finnish (FIN) AF: 1.00 AC: 4 AN: 4

Middle Eastern (MID) AC: 0 AN: 0

European-Non Finnish (NFE) AF: 0.843 AC: 145 AN: 172

Other (OTH) AF: 1.00 AC: 6 AN: 6

GnomAD4 genome AF: 0.828 AC: 125827 AN: 151908 Hom.: 52503 Cov.: 30 AF XY: 0.834 AC XY: 61885 AN XY: 74240

African (AFR) AF: 0.712 AC: 29487 AN: 41396

American (AMR) AF: 0.909 AC: 13909 AN: 15296

Ashkenazi Jewish (ASJ) AF: 0.849 AC: 2948 AN: 3472

East Asian (EAS) AF: 0.848 AC: 4294 AN: 5064

South Asian (SAS) AF: 0.866 AC: 4165 AN: 4808

European-Finnish (FIN) AF: 0.929 AC: 9855 AN: 10610

Middle Eastern (MID) AF: 0.857 AC: 252 AN: 294

European-Non Finnish (NFE) AF: 0.858 AC: 58331 AN: 67952

Other (OTH) AF: 0.863 AC: 1818 AN: 2106

Alfa AF: 0.849 Hom.: 25120

Bravo AF: 0.822

Asia WGS AF: 0.835 AC: 2902 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.89
CADD	Benign	2.0
DANN	Benign	0.31
PhyloP100		-1.4

Splicing

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

Other links and lift over

dbSNP: rs2839685; hg19: chr10-44881638;