chr10-44373578-C-T

Variant names:

• chr10-44373578-C-T
• rs3780890
• ENST00000374429.6:c.267-235G>A

Variant summary

Our verdict is Benign. The variant received -14 ACMG points: 0P and 14B. BP4_Strong BP6_Moderate BA1

The NM_001277990.2(CXCL12):​c.110-488G>A variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.193 in 152,202 control chromosomes in the GnomAD database, including 3,240 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★).

• Frequency: Genomes: 𝑓 0.19 (3240 hom., cov: 33)
• Consequence: CXCL12 NM_001277990.2 intron
• Clinical Significance: Benign criteria provided, single submitter B:1
• Conservation: PhyloP100: -0.785
• Publications: 2 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 -14 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.86).
• BP6: Variant 10-44373578-C-T is Benign according to our data. Variant chr10-44373578-C-T is described in ClinVar as Benign. ClinVar VariationId is 1272932.Status of the report is criteria_provided_single_submitter, 1 stars.
• BA1: GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.423 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.110-488G>A		intron	N/A	NP_001264919.1	P48061-7
	CXCL12	NM_000609.7		c.267-235G>A		intron	N/A	NP_000600.1	P48061-1

Ensembl Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	CXCL12	ENST00000374429.6	TSL:1	c.267-235G>A		intron	N/A	ENSP00000363551.2	P48061-1
	CXCL12	ENST00000395793.7	TSL:5	c.110-488G>A		intron	N/A	ENSP00000379139.3	P48061-7

Frequencies

GnomAD3 genomes AF: 0.193 AC: 29319 AN: 152082 Hom.: 3229 Cov.: 33

Gnomad AFR AF: 0.109

Gnomad AMI AF: 0.222

Gnomad AMR AF: 0.199

Gnomad ASJ AF: 0.249

Gnomad EAS AF: 0.438

Gnomad SAS AF: 0.275

Gnomad FIN AF: 0.203

Gnomad MID AF: 0.334

Gnomad NFE AF: 0.211

Gnomad OTH AF: 0.220

We have no GnomAD4 exomes data on this position. Probably position not covered by the project.

GnomAD4 genome AF: 0.193 AC: 29344 AN: 152202 Hom.: 3240 Cov.: 33 AF XY: 0.195 AC XY: 14538 AN XY: 74412

African (AFR) AF: 0.109 AC: 4544 AN: 41548

American (AMR) AF: 0.199 AC: 3046 AN: 15304

Ashkenazi Jewish (ASJ) AF: 0.249 AC: 866 AN: 3472

East Asian (EAS) AF: 0.438 AC: 2263 AN: 5162

South Asian (SAS) AF: 0.274 AC: 1324 AN: 4824

European-Finnish (FIN) AF: 0.203 AC: 2152 AN: 10592

Middle Eastern (MID) AF: 0.329 AC: 96 AN: 292

European-Non Finnish (NFE) AF: 0.211 AC: 14368 AN: 67982

Other (OTH) AF: 0.228 AC: 483 AN: 2116

Alfa AF: 0.123 Hom.: 264

Bravo AF: 0.187

Asia WGS AF: 0.360 AC: 1250 AN: 3478

ClinVar

ClinVar submissions

Significance: Benign

Revision: criteria provided, single submitter

Pathogenic	VUS	Benign	Condition
-	-	1	not provided (1)

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.86
CADD	Benign	1.0
DANN	Benign	0.72
PhyloP100		-0.79
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: rs3780890; hg19: chr10-44869026;