10-44384928-C-T

Variant names:

• chr10-44384928-C-T
• rs17540465
• NM_199168.4:c.61+17G>A

Variant summary

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

The NM_199168.4(CXCL12):​c.61+17G>A variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.036 in 1,541,632 control chromosomes in the GnomAD database, including 1,205 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★★).

• Frequency:
  • Genomes: 𝑓 0.050 (222 hom., cov: 31)
  • Exomes 𝑓: 0.035 (983 hom.)
• Consequence: CXCL12 NM_199168.4 intron
• Clinical Significance: Benign criteria provided, multiple submitters, no conflicts B:2
• Conservation: PhyloP100: -0.401
• 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]

ENSG00000303087 (HGNC:):

ACMG classification

Our verdict: Benign. The variant received -20 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.76).
• BP6: Variant 10-44384928-C-T is Benign according to our data. Variant chr10-44384928-C-T is described in ClinVar as Benign. ClinVar VariationId is 1273360.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars.
• BA1: GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.0918 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+17G>A		intron	N/A	NP_954637.1	P48061-2
	CXCL12	NM_001178134.2		c.61+17G>A		intron	N/A	NP_001171605.1	P48061-4
	CXCL12	NM_001033886.2		c.61+17G>A		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+17G>A		intron	N/A	ENSP00000339913.6	P48061-2
	CXCL12	ENST00000395794.2	TSL:1	c.61+17G>A		intron	N/A	ENSP00000379140.2	P48061-4
	CXCL12	ENST00000374426.6	TSL:1	c.61+17G>A		intron	N/A	ENSP00000363548.2	P48061-3

Frequencies

GnomAD3 genomes AF: 0.0499 AC: 7335 AN: 147132 Hom.: 222 Cov.: 31

Gnomad AFR AF: 0.0944

Gnomad AMI AF: 0.0692

Gnomad AMR AF: 0.0392

Gnomad ASJ AF: 0.0151

Gnomad EAS AF: 0.0561

Gnomad SAS AF: 0.0599

Gnomad FIN AF: 0.0202

Gnomad MID AF: 0.0294

Gnomad NFE AF: 0.0332

Gnomad OTH AF: 0.0399

GnomAD2 exomes AF: 0.0415 AC: 6520 AN: 157008 AF XY: 0.0420

Gnomad AFR exome AF: 0.0915

Gnomad AMR exome AF: 0.0459

Gnomad ASJ exome AF: 0.0177

Gnomad EAS exome AF: 0.0609

Gnomad FIN exome AF: 0.0204

Gnomad NFE exome AF: 0.0331

Gnomad OTH exome AF: 0.0372

GnomAD4 exome AF: 0.0346 AC: 48197 AN: 1394392 Hom.: 983 Cov.: 33 AF XY: 0.0354 AC XY: 24449 AN XY: 691126

African (AFR) AF: 0.0822 AC: 2408 AN: 29306

American (AMR) AF: 0.0452 AC: 1783 AN: 39432

Ashkenazi Jewish (ASJ) AF: 0.0161 AC: 399 AN: 24748

East Asian (EAS) AF: 0.0428 AC: 1504 AN: 35104

South Asian (SAS) AF: 0.0577 AC: 4580 AN: 79412

European-Finnish (FIN) AF: 0.0220 AC: 781 AN: 35566

Middle Eastern (MID) AF: 0.0529 AC: 243 AN: 4596

European-Non Finnish (NFE) AF: 0.0315 AC: 34249 AN: 1088240

Other (OTH) AF: 0.0388 AC: 2250 AN: 57988

GnomAD4 genome AF: 0.0499 AC: 7347 AN: 147240 Hom.: 222 Cov.: 31 AF XY: 0.0489 AC XY: 3523 AN XY: 72112

African (AFR) AF: 0.0944 AC: 3508 AN: 37158

American (AMR) AF: 0.0392 AC: 592 AN: 15086

Ashkenazi Jewish (ASJ) AF: 0.0151 AC: 51 AN: 3374

East Asian (EAS) AF: 0.0559 AC: 287 AN: 5134

South Asian (SAS) AF: 0.0606 AC: 292 AN: 4818

European-Finnish (FIN) AF: 0.0202 AC: 214 AN: 10590

Middle Eastern (MID) AF: 0.0352 AC: 10 AN: 284

European-Non Finnish (NFE) AF: 0.0332 AC: 2250 AN: 67836

Other (OTH) AF: 0.0390 AC: 80 AN: 2050

Alfa AF: 0.0393 Hom.: 32

Bravo AF: 0.0508

Asia WGS AF: 0.0590 AC: 205 AN: 3468

ClinVar

ClinVar submissions

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	-0.76
CADD	Benign	8.8
DANN	Benign	0.84
PhyloP100		-0.40
PromoterAI		-0.011	Neutral
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: rs17540465; hg19: chr10-44880376;