10-44378805-C-T

Variant names:

• chr10-44378805-C-T
• rs266085
• NM_199168.4:c.180-82G>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.180-82G>A variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.353 in 1,376,336 control chromosomes in the GnomAD database, including 88,365 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★★).

• Frequency:
  • Genomes: 𝑓 0.33 (8564 hom., cov: 33)
  • Exomes 𝑓: 0.36 (79801 hom.)
• Consequence: CXCL12 NM_199168.4 intron
• Clinical Significance: Benign criteria provided, multiple submitters, no conflicts B:2
• Conservation: PhyloP100: -0.847
• Publications: 17 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=-0.85).
• BP6: Variant 10-44378805-C-T is Benign according to our data. Variant chr10-44378805-C-T is described in ClinVar as Benign. ClinVar VariationId is 1284236.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars.
• BA1: GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.535 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.180-82G>A		intron	N/A	NP_954637.1	P48061-2
	CXCL12	NM_001178134.2		c.180-82G>A		intron	N/A	NP_001171605.1	P48061-4
	CXCL12	NM_001033886.2		c.180-82G>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.180-82G>A		intron	N/A	ENSP00000339913.6	P48061-2
	CXCL12	ENST00000395794.2	TSL:1	c.180-82G>A		intron	N/A	ENSP00000379140.2	P48061-4
	CXCL12	ENST00000374426.6	TSL:1	c.180-82G>A		intron	N/A	ENSP00000363548.2	P48061-3

Frequencies

GnomAD3 genomes AF: 0.325 AC: 49409 AN: 151958 Hom.: 8555 Cov.: 33

Gnomad AFR AF: 0.226

Gnomad AMI AF: 0.300

Gnomad AMR AF: 0.321

Gnomad ASJ AF: 0.409

Gnomad EAS AF: 0.551

Gnomad SAS AF: 0.439

Gnomad FIN AF: 0.319

Gnomad MID AF: 0.500

Gnomad NFE AF: 0.356

Gnomad OTH AF: 0.366

GnomAD4 exome AF: 0.356 AC: 436117 AN: 1224260 Hom.: 79801 AF XY: 0.361 AC XY: 223789 AN XY: 620146

African (AFR) AF: 0.225 AC: 6470 AN: 28814

American (AMR) AF: 0.298 AC: 13075 AN: 43924

Ashkenazi Jewish (ASJ) AF: 0.402 AC: 9889 AN: 24576

East Asian (EAS) AF: 0.568 AC: 21808 AN: 38428

South Asian (SAS) AF: 0.426 AC: 34623 AN: 81268

European-Finnish (FIN) AF: 0.326 AC: 16731 AN: 51370

Middle Eastern (MID) AF: 0.472 AC: 2256 AN: 4784

European-Non Finnish (NFE) AF: 0.347 AC: 311920 AN: 898704

Other (OTH) AF: 0.369 AC: 19345 AN: 52392

GnomAD4 genome AF: 0.325 AC: 49447 AN: 152076 Hom.: 8564 Cov.: 33 AF XY: 0.326 AC XY: 24240 AN XY: 74338

African (AFR) AF: 0.226 AC: 9386 AN: 41482

American (AMR) AF: 0.321 AC: 4905 AN: 15280

Ashkenazi Jewish (ASJ) AF: 0.409 AC: 1418 AN: 3470

East Asian (EAS) AF: 0.552 AC: 2847 AN: 5160

South Asian (SAS) AF: 0.439 AC: 2116 AN: 4824

European-Finnish (FIN) AF: 0.319 AC: 3380 AN: 10582

Middle Eastern (MID) AF: 0.486 AC: 142 AN: 292

European-Non Finnish (NFE) AF: 0.356 AC: 24192 AN: 67962

Other (OTH) AF: 0.373 AC: 787 AN: 2112

Alfa AF: 0.330 Hom.: 1939

Bravo AF: 0.319

Asia WGS AF: 0.462 AC: 1605 AN: 3478

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	-0.85
CADD	Benign	2.8
DANN	Benign	0.87
PhyloP100		-0.85
Mutation Taster		=100/0	polymorphism (auto)

Splicing

Name	Calibrated prediction	Score	Prediction
SpliceAI score (max)		0.010		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: rs266085; hg19: chr10-44874253;