rs266091

Variant names:

• chr10-44373408-A-C
• rs266091
• ENST00000374429.6:c.267-65T>G

Your query was ambiguous. Multiple possible variants found:

• chr10-44373408-A-C
• chr10-44373408-A-G

Variant summary

Our verdict is Benign. The variant received -20 ACMG points: 0P and 20B. BP4_Strong BP6_Very_Strong BA1

The NM_001277990.2(CXCL12):​c.110-318T>G variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.855 in 1,449,630 control chromosomes in the GnomAD database, including 530,960 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★★).

• Frequency:
  • Genomes: 𝑓 0.84 (53777 hom., cov: 34)
  • Exomes 𝑓: 0.86 (477183 hom.)
• Consequence: CXCL12 NM_001277990.2 intron
• Clinical Significance: Benign criteria provided, multiple submitters, no conflicts B:2
• Conservation: PhyloP100: -0.497
• Publications: 6 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 -20 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.91).
• BP6: Variant 10-44373408-A-C is Benign according to our data. Variant chr10-44373408-A-C is described in ClinVar as Benign. ClinVar VariationId is 1280296.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars.
• BA1: GnomAd4 highest subpopulation (AMR) allele frequency at 95% confidence interval = 0.902 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.110-318T>G		intron	N/A	NP_001264919.1
	CXCL12	NM_000609.7		c.267-65T>G		intron	N/A	NP_000600.1

Ensembl Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	CXCL12	ENST00000374429.6	TSL:1	c.267-65T>G		intron	N/A	ENSP00000363551.2
	CXCL12	ENST00000395793.7	TSL:5	c.110-318T>G		intron	N/A	ENSP00000379139.3

Frequencies

GnomAD3 genomes AF: 0.838 AC: 127537 AN: 152120 Hom.: 53730 Cov.: 34

Gnomad AFR AF: 0.741

Gnomad AMI AF: 0.848

Gnomad AMR AF: 0.914

Gnomad ASJ AF: 0.850

Gnomad EAS AF: 0.864

Gnomad SAS AF: 0.850

Gnomad FIN AF: 0.934

Gnomad MID AF: 0.848

Gnomad NFE AF: 0.861

Gnomad OTH AF: 0.868

GnomAD4 exome AF: 0.857 AC: 1111998 AN: 1297392 Hom.: 477183 AF XY: 0.857 AC XY: 557043 AN XY: 649856

African (AFR) AF: 0.739 AC: 22101 AN: 29898

American (AMR) AF: 0.927 AC: 36920 AN: 39812

Ashkenazi Jewish (ASJ) AF: 0.858 AC: 21105 AN: 24608

East Asian (EAS) AF: 0.842 AC: 31359 AN: 37224

South Asian (SAS) AF: 0.853 AC: 67027 AN: 78554

European-Finnish (FIN) AF: 0.922 AC: 47265 AN: 51288

Middle Eastern (MID) AF: 0.868 AC: 4769 AN: 5494

European-Non Finnish (NFE) AF: 0.855 AC: 834327 AN: 975586

Other (OTH) AF: 0.858 AC: 47125 AN: 54928

GnomAD4 genome AF: 0.838 AC: 127638 AN: 152238 Hom.: 53777 Cov.: 34 AF XY: 0.843 AC XY: 62768 AN XY: 74422

African (AFR) AF: 0.742 AC: 30803 AN: 41530

American (AMR) AF: 0.915 AC: 13998 AN: 15306

Ashkenazi Jewish (ASJ) AF: 0.850 AC: 2952 AN: 3472

East Asian (EAS) AF: 0.864 AC: 4446 AN: 5148

South Asian (SAS) AF: 0.849 AC: 4099 AN: 4828

European-Finnish (FIN) AF: 0.934 AC: 9922 AN: 10624

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

European-Non Finnish (NFE) AF: 0.861 AC: 58555 AN: 68010

Other (OTH) AF: 0.869 AC: 1838 AN: 2114

Alfa AF: 0.842 Hom.: 7408

Bravo AF: 0.834

Asia WGS AF: 0.836 AC: 2905 AN: 3478

ClinVar

ClinVar submissions as Germline

Significance: Benign

Revision: criteria provided, multiple submitters, no conflicts

Pathogenic	VUS	Benign	Condition
-	-	2	not provided (2)

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.91
CADD	Benign	1.5
DANN	Benign	0.49
PhyloP100		-0.50
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: rs266091; hg19: chr10-44868856; COSMIC: COSV59107387; COSMIC: COSV59107387;