rs7092453

Variant names:

• chr10-44383384-T-C
• rs7092453
• NM_199168.4:c.61+1561A>G

Your query was ambiguous. Multiple possible variants found:

• chr10-44383384-T-C
• chr10-44383384-T-G

Variant summary

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

The NM_199168.4(CXCL12):​c.61+1561A>G variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.184 in 151,992 control chromosomes in the GnomAD database, including 2,707 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 0.18 (2707 hom., cov: 31)
• Consequence: CXCL12 NM_199168.4 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -1.37
• 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]

ACMG classification

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

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.8).
• BA1: GnomAd4 highest subpopulation (NFE) allele frequency at 95% confidence interval = 0.206 is higher than 0.05.

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_199168.4. 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_199168.4	MANE Select	c.61+1561A>G		intron	N/A	NP_954637.1	P48061-2
	CXCL12	NM_001178134.2		c.61+1561A>G		intron	N/A	NP_001171605.1	P48061-4
	CXCL12	NM_001033886.2		c.61+1561A>G		intron	N/A	NP_001029058.1	P48061-3

Ensembl Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	CXCL12	ENST00000343575.11	TSL:1 MANE Select	c.61+1561A>G		intron	N/A	ENSP00000339913.6	P48061-2
	CXCL12	ENST00000395794.2	TSL:1	c.61+1561A>G		intron	N/A	ENSP00000379140.2	P48061-4
	CXCL12	ENST00000374426.6	TSL:1	c.61+1561A>G		intron	N/A	ENSP00000363548.2	P48061-3

Frequencies

GnomAD3 genomes AF: 0.184 AC: 27937 AN: 151874 Hom.: 2706 Cov.: 31

Gnomad AFR AF: 0.190

Gnomad AMI AF: 0.163

Gnomad AMR AF: 0.142

Gnomad ASJ AF: 0.184

Gnomad EAS AF: 0.00194

Gnomad SAS AF: 0.0539

Gnomad FIN AF: 0.214

Gnomad MID AF: 0.114

Gnomad NFE AF: 0.209

Gnomad OTH AF: 0.176

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

GnomAD4 genome AF: 0.184 AC: 27944 AN: 151992 Hom.: 2707 Cov.: 31 AF XY: 0.180 AC XY: 13366 AN XY: 74300

African (AFR) AF: 0.190 AC: 7879 AN: 41474

American (AMR) AF: 0.142 AC: 2174 AN: 15284

Ashkenazi Jewish (ASJ) AF: 0.184 AC: 638 AN: 3464

East Asian (EAS) AF: 0.00195 AC: 10 AN: 5136

South Asian (SAS) AF: 0.0533 AC: 256 AN: 4802

European-Finnish (FIN) AF: 0.214 AC: 2267 AN: 10578

Middle Eastern (MID) AF: 0.122 AC: 36 AN: 294

European-Non Finnish (NFE) AF: 0.209 AC: 14168 AN: 67936

Other (OTH) AF: 0.174 AC: 367 AN: 2112

Alfa AF: 0.199 Hom.: 530

Bravo AF: 0.179

Asia WGS AF: 0.0430 AC: 152 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.80
CADD	Benign	8.3
DANN	Benign	0.80
PhyloP100		-1.4
Mutation Taster		=100/0	polymorphism (auto)

Splicing

Name	Calibrated prediction	Score	Prediction
SpliceAI score (max)		0.0		Details are displayed if max score is > 0.2

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

Other links and lift over

dbSNP: rs7092453; hg19: chr10-44878832;