10-44374567-C-T

Variant names:

• chr10-44374567-C-T
• rs266088
• ENST00000374429.6:c.267-1224G>A

Variant summary

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

The NM_001277990.2(CXCL12):​c.110-1477G>A variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.139 in 455,868 control chromosomes in the GnomAD database, including 4,578 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 0.13 (1346 hom., cov: 33)
  • Exomes 𝑓: 0.14 (3232 hom.)
• Consequence: CXCL12 NM_001277990.2 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -3.42
• Publications: 8 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]

ACMG classification

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

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.9).
• BA1: GnomAd4 highest subpopulation (SAS) allele frequency at 95% confidence interval = 0.156 is higher than 0.05.

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_001277990.2. 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
	CXCL12	NM_001277990.2		c.110-1477G>A		intron	N/A	NP_001264919.1	P48061-7
	CXCL12	NM_000609.7		c.267-1224G>A		intron	N/A	NP_000600.1	P48061-1

Ensembl Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	CXCL12	ENST00000374429.6	TSL:1	c.267-1224G>A		intron	N/A	ENSP00000363551.2	P48061-1
	CXCL12	ENST00000395793.7	TSL:5	c.110-1477G>A		intron	N/A	ENSP00000379139.3	P48061-7

Frequencies

GnomAD3 genomes AF: 0.130 AC: 19772 AN: 151988 Hom.: 1350 Cov.: 33

Gnomad AFR AF: 0.111

Gnomad AMI AF: 0.0789

Gnomad AMR AF: 0.124

Gnomad ASJ AF: 0.148

Gnomad EAS AF: 0.104

Gnomad SAS AF: 0.165

Gnomad FIN AF: 0.116

Gnomad MID AF: 0.165

Gnomad NFE AF: 0.144

Gnomad OTH AF: 0.143

GnomAD2 exomes AF: 0.137 AC: 17608 AN: 128104 AF XY: 0.141

Gnomad AFR exome AF: 0.113

Gnomad AMR exome AF: 0.110

Gnomad ASJ exome AF: 0.147

Gnomad EAS exome AF: 0.0981

Gnomad FIN exome AF: 0.113

Gnomad NFE exome AF: 0.147

Gnomad OTH exome AF: 0.152

GnomAD4 exome AF: 0.143 AC: 43564 AN: 303762 Hom.: 3232 Cov.: 0 AF XY: 0.147 AC XY: 25488 AN XY: 172984

African (AFR) AF: 0.113 AC: 974 AN: 8620

American (AMR) AF: 0.110 AC: 2998 AN: 27274

Ashkenazi Jewish (ASJ) AF: 0.150 AC: 1621 AN: 10786

East Asian (EAS) AF: 0.105 AC: 968 AN: 9210

South Asian (SAS) AF: 0.173 AC: 10357 AN: 59736

European-Finnish (FIN) AF: 0.114 AC: 1416 AN: 12368

Middle Eastern (MID) AF: 0.151 AC: 418 AN: 2776

European-Non Finnish (NFE) AF: 0.144 AC: 22837 AN: 158776

Other (OTH) AF: 0.139 AC: 1975 AN: 14216

GnomAD4 genome AF: 0.130 AC: 19779 AN: 152106 Hom.: 1346 Cov.: 33 AF XY: 0.129 AC XY: 9555 AN XY: 74340

African (AFR) AF: 0.111 AC: 4601 AN: 41490

American (AMR) AF: 0.123 AC: 1887 AN: 15280

Ashkenazi Jewish (ASJ) AF: 0.148 AC: 513 AN: 3472

East Asian (EAS) AF: 0.104 AC: 537 AN: 5160

South Asian (SAS) AF: 0.165 AC: 795 AN: 4816

European-Finnish (FIN) AF: 0.116 AC: 1226 AN: 10584

Middle Eastern (MID) AF: 0.156 AC: 46 AN: 294

European-Non Finnish (NFE) AF: 0.144 AC: 9803 AN: 67988

Other (OTH) AF: 0.142 AC: 299 AN: 2110

Alfa AF: 0.136 Hom.: 1943

Bravo AF: 0.128

Asia WGS AF: 0.101 AC: 351 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.90
CADD	Benign	0.021
DANN	Benign	0.51
PhyloP100		-3.4
Mutation Taster		=100/0	polymorphism (auto)

Splicing

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

Other links and lift over

dbSNP: rs266088; hg19: chr10-44870015; COSMIC: COSV59107466; COSMIC: COSV59107466;