rs17880170

Variant names:

• chr10-44377752-C-A
• rs17880170
• ENST00000395794.2:c.420G>T

Your query was ambiguous. Multiple possible variants found:

• chr10-44377752-C-A
• chr10-44377752-C-G
• chr10-44377752-C-T

Variant summary

Our verdict is Benign. The variant received -11 ACMG points: 0P and 11B. BP4_Strong BP6_Moderate BP7 BS2

The NM_001178134.2(CXCL12):​c.420G>T​(p.Val140Val) variant causes a synonymous change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00596 in 1,598,366 control chromosomes in the GnomAD database, including 46 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Likely benign (★).

• Frequency:
  • Genomes: 𝑓 0.0051 (6 hom., cov: 33)
  • Exomes 𝑓: 0.0060 (40 hom.)
• Consequence: CXCL12 NM_001178134.2 synonymous
• Clinical Significance: Likely benign criteria provided, single submitter B:2
• Conservation: PhyloP100: -0.101
• Publications: 1 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 -11 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.83).
• BP6: Variant 10-44377752-C-A is Benign according to our data. Variant chr10-44377752-C-A is described in ClinVar as Likely_benign. ClinVar VariationId is 2640421.Status of the report is criteria_provided_single_submitter, 1 stars.
• BP7: Synonymous conserved (PhyloP=-0.101 with no splicing effect.
• BS2: High Homozygotes in GnomAd4 at 6 gene

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_001178134.2. 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_199168.4	MANE Select	c.*881G>T		3_prime_UTR	Exon 3 of 3	NP_954637.1	P48061-2
	CXCL12	NM_001178134.2		c.420G>T	p.Val140Val	synonymous	Exon 4 of 4	NP_001171605.1	P48061-4
	CXCL12	NM_001033886.2		c.266+885G>T		intron	N/A	NP_001029058.1	P48061-3

Ensembl Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	CXCL12	ENST00000395794.2	TSL:1	c.420G>T	p.Val140Val	synonymous	Exon 4 of 4	ENSP00000379140.2	P48061-4
	CXCL12	ENST00000343575.11	TSL:1 MANE Select	c.*881G>T		3_prime_UTR	Exon 3 of 3	ENSP00000339913.6	P48061-2
	CXCL12	ENST00000374426.6	TSL:1	c.266+885G>T		intron	N/A	ENSP00000363548.2	P48061-3

Frequencies

GnomAD3 genomes AF: 0.00516 AC: 785 AN: 152224 Hom.: 6 Cov.: 33

Gnomad AFR AF: 0.00133

Gnomad AMI AF: 0.0406

Gnomad AMR AF: 0.00445

Gnomad ASJ AF: 0.0507

Gnomad EAS AF: 0.00

Gnomad SAS AF: 0.000207

Gnomad FIN AF: 0.00160

Gnomad MID AF: 0.00

Gnomad NFE AF: 0.00620

Gnomad OTH AF: 0.00430

GnomAD2 exomes AF: 0.00557 AC: 1288 AN: 231434 AF XY: 0.00541

Gnomad AFR exome AF: 0.00144

Gnomad AMR exome AF: 0.00213

Gnomad ASJ exome AF: 0.0404

Gnomad EAS exome AF: 0.00

Gnomad FIN exome AF: 0.00206

Gnomad NFE exome AF: 0.00673

Gnomad OTH exome AF: 0.00733

GnomAD4 exome AF: 0.00605 AC: 8748 AN: 1446024 Hom.: 40 Cov.: 32 AF XY: 0.00595 AC XY: 4282 AN XY: 719716

African (AFR) AF: 0.00102 AC: 34 AN: 33476

American (AMR) AF: 0.00228 AC: 102 AN: 44714

Ashkenazi Jewish (ASJ) AF: 0.0416 AC: 1086 AN: 26134

East Asian (EAS) AF: 0.0000504 AC: 2 AN: 39692

South Asian (SAS) AF: 0.000197 AC: 17 AN: 86220

European-Finnish (FIN) AF: 0.00268 AC: 102 AN: 38014

Middle Eastern (MID) AF: 0.00191 AC: 11 AN: 5750

European-Non Finnish (NFE) AF: 0.00627 AC: 6970 AN: 1111748

Other (OTH) AF: 0.00703 AC: 424 AN: 60276

GnomAD4 genome AF: 0.00515 AC: 784 AN: 152342 Hom.: 6 Cov.: 33 AF XY: 0.00486 AC XY: 362 AN XY: 74494

African (AFR) AF: 0.00132 AC: 55 AN: 41574

American (AMR) AF: 0.00444 AC: 68 AN: 15304

Ashkenazi Jewish (ASJ) AF: 0.0507 AC: 176 AN: 3470

East Asian (EAS) AF: 0.00 AC: 0 AN: 5188

South Asian (SAS) AF: 0.000207 AC: 1 AN: 4832

European-Finnish (FIN) AF: 0.00160 AC: 17 AN: 10620

Middle Eastern (MID) AF: 0.00 AC: 0 AN: 294

European-Non Finnish (NFE) AF: 0.00619 AC: 421 AN: 68032

Other (OTH) AF: 0.00425 AC: 9 AN: 2116

Alfa AF: 0.00629 Hom.: 11

Bravo AF: 0.00530

EpiCase AF: 0.00649

EpiControl AF: 0.00718

ClinVar

ClinVar submissions

Significance: Likely benign

Revision: criteria provided, single submitter

Pathogenic	VUS	Benign	Condition
-	-	1	CXCL12-related disorder (1)
-	-	1	not provided (1)

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.83
CADD	Benign	3.1
DANN	Benign	0.49
PhyloP100		-0.10
Mutation Taster		=100/0	polymorphism

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: rs17880170; hg19: chr10-44873200;