rs2297630

Variant names:

• chr10-44376100-G-A
• rs2297630
• ENST00000374426.6:c.267-68C>T

Your query was ambiguous. Multiple possible variants found:

• chr10-44376100-G-A
• chr10-44376100-G-C
• chr10-44376100-G-T

Variant summary

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

The ENST00000374426.6(CXCL12):​c.267-68C>T variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.257 in 1,561,326 control chromosomes in the GnomAD database, including 55,135 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★★).

• Frequency:
  • Genomes: 𝑓 0.22 (4529 hom., cov: 34)
  • Exomes 𝑓: 0.26 (50606 hom.)
• Consequence: CXCL12 ENST00000374426.6 intron
• Clinical Significance: Benign criteria provided, multiple submitters, no conflicts B:2
• Conservation: PhyloP100: -2.11
• Publications: 35 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=-0.83).
• BP6: Variant 10-44376100-G-A is Benign according to our data. Variant chr10-44376100-G-A is described in ClinVar as Benign. ClinVar VariationId is 1250974.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars.
• BA1: GnomAd4 highest subpopulation (AMR) allele frequency at 95% confidence interval = 0.377 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
CXCL12	NM_001033886.2	c.267-68C>T		intron_variant	Intron 3 of 3		NP_001029058.1
CXCL12	NM_001277990.2	c.110-3010C>T		intron_variant	Intron 2 of 2		NP_001264919.1
CXCL12	NM_000609.7	c.266+2537C>T		intron_variant	Intron 3 of 3		NP_000600.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
CXCL12	ENST00000374426.6	c.267-68C>T		intron_variant	Intron 3 of 3	1		ENSP00000363548.2
CXCL12	ENST00000374429.6	c.266+2537C>T		intron_variant	Intron 3 of 3	1		ENSP00000363551.2
CXCL12	ENST00000395793.7	c.110-3010C>T		intron_variant	Intron 2 of 2	5		ENSP00000379139.3

Frequencies

GnomAD3 genomes AF: 0.217 AC: 32942 AN: 152050 Hom.: 4528 Cov.: 34

Gnomad AFR AF: 0.0601

Gnomad AMI AF: 0.282

Gnomad AMR AF: 0.385

Gnomad ASJ AF: 0.233

Gnomad EAS AF: 0.136

Gnomad SAS AF: 0.220

Gnomad FIN AF: 0.341

Gnomad MID AF: 0.190

Gnomad NFE AF: 0.258

Gnomad OTH AF: 0.246

GnomAD4 exome AF: 0.262 AC: 368668 AN: 1409158 Hom.: 50606 AF XY: 0.260 AC XY: 182597 AN XY: 703050

African (AFR) AF: 0.0474 AC: 1496 AN: 31586

American (AMR) AF: 0.472 AC: 19650 AN: 41634

Ashkenazi Jewish (ASJ) AF: 0.237 AC: 6011 AN: 25388

East Asian (EAS) AF: 0.138 AC: 5416 AN: 39388

South Asian (SAS) AF: 0.233 AC: 19177 AN: 82426

European-Finnish (FIN) AF: 0.324 AC: 16317 AN: 50286

Middle Eastern (MID) AF: 0.180 AC: 1011 AN: 5630

European-Non Finnish (NFE) AF: 0.266 AC: 285393 AN: 1074322

Other (OTH) AF: 0.243 AC: 14197 AN: 58498

GnomAD4 genome AF: 0.216 AC: 32941 AN: 152168 Hom.: 4529 Cov.: 34 AF XY: 0.223 AC XY: 16622 AN XY: 74380

African (AFR) AF: 0.0599 AC: 2491 AN: 41556

American (AMR) AF: 0.386 AC: 5897 AN: 15292

Ashkenazi Jewish (ASJ) AF: 0.233 AC: 809 AN: 3468

East Asian (EAS) AF: 0.135 AC: 700 AN: 5178

South Asian (SAS) AF: 0.219 AC: 1055 AN: 4820

European-Finnish (FIN) AF: 0.341 AC: 3603 AN: 10564

Middle Eastern (MID) AF: 0.197 AC: 58 AN: 294

European-Non Finnish (NFE) AF: 0.258 AC: 17557 AN: 67978

Other (OTH) AF: 0.244 AC: 514 AN: 2108

Alfa AF: 0.250 Hom.: 9296

Bravo AF: 0.216

Asia WGS AF: 0.176 AC: 611 AN: 3478

ClinVar

Significance: Benign

Submissions summary: Benign:2

Revision: criteria provided, multiple submitters, no conflicts

Submissions by phenotype

not provided Benign:2

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Breakthrough Genomics, Breakthrough Genomics

Significance: Benign

Review Status: criteria provided, single submitter

Collection Method: not provided

- -

Nov 10, 2018

GeneDx

Significance: Benign

Review Status: criteria provided, single submitter

Collection Method: clinical testing

- -

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.83
CADD	Benign	0.58
DANN	Benign	0.71
PhyloP100		-2.1
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: rs2297630; hg19: chr10-44871548;