NM_199168.4:c.180-138C>A

Variant names:

• chr10-44378861-G-T
• rs2236534
• NM_199168.4:c.180-138C>A

Variant summary

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

The NM_199168.4(CXCL12):​c.180-138C>A variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.192 in 797,266 control chromosomes in the GnomAD database, including 16,460 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★).

• Frequency:
  • Genomes: 𝑓 0.17 (2738 hom., cov: 33)
  • Exomes 𝑓: 0.20 (13722 hom.)
• Consequence: CXCL12 NM_199168.4 intron
• Clinical Significance: Benign criteria provided, single submitter B:1
• Conservation: PhyloP100: 0.985
• Publications: 9 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=-0.8).
• BP6: Variant 10-44378861-G-T is Benign according to our data. Variant chr10-44378861-G-T is described in ClinVar as Benign. ClinVar VariationId is 1234302.Status of the report is criteria_provided_single_submitter, 1 stars.
• BA1: GnomAd4 highest subpopulation (AMR) allele frequency at 95% confidence interval = 0.315 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
CXCL12	NM_199168.4	c.180-138C>A		intron_variant	Intron 2 of 2	ENST00000343575.11	NP_954637.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
CXCL12	ENST00000343575.11	c.180-138C>A		intron_variant	Intron 2 of 2	1	NM_199168.4	ENSP00000339913.6

Frequencies

GnomAD3 genomes AF: 0.166 AC: 25250 AN: 152124 Hom.: 2737 Cov.: 33

Gnomad AFR AF: 0.0420

Gnomad AMI AF: 0.134

Gnomad AMR AF: 0.322

Gnomad ASJ AF: 0.176

Gnomad EAS AF: 0.135

Gnomad SAS AF: 0.108

Gnomad FIN AF: 0.230

Gnomad MID AF: 0.133

Gnomad NFE AF: 0.202

Gnomad OTH AF: 0.205

GnomAD4 exome AF: 0.198 AC: 128000 AN: 645024 Hom.: 13722 AF XY: 0.194 AC XY: 65890 AN XY: 340106

African (AFR) AF: 0.0381 AC: 660 AN: 17326

American (AMR) AF: 0.385 AC: 12591 AN: 32724

Ashkenazi Jewish (ASJ) AF: 0.181 AC: 3280 AN: 18124

East Asian (EAS) AF: 0.138 AC: 4667 AN: 33742

South Asian (SAS) AF: 0.123 AC: 7321 AN: 59688

European-Finnish (FIN) AF: 0.229 AC: 8768 AN: 38240

Middle Eastern (MID) AF: 0.143 AC: 363 AN: 2530

European-Non Finnish (NFE) AF: 0.205 AC: 84161 AN: 409850

Other (OTH) AF: 0.189 AC: 6189 AN: 32800

GnomAD4 genome AF: 0.166 AC: 25250 AN: 152242 Hom.: 2738 Cov.: 33 AF XY: 0.169 AC XY: 12608 AN XY: 74434

African (AFR) AF: 0.0418 AC: 1738 AN: 41552

American (AMR) AF: 0.322 AC: 4929 AN: 15292

Ashkenazi Jewish (ASJ) AF: 0.176 AC: 611 AN: 3470

East Asian (EAS) AF: 0.134 AC: 693 AN: 5170

South Asian (SAS) AF: 0.107 AC: 516 AN: 4830

European-Finnish (FIN) AF: 0.230 AC: 2436 AN: 10594

Middle Eastern (MID) AF: 0.143 AC: 42 AN: 294

European-Non Finnish (NFE) AF: 0.202 AC: 13734 AN: 68016

Other (OTH) AF: 0.203 AC: 429 AN: 2114

Alfa AF: 0.149 Hom.: 1474

Bravo AF: 0.171

Asia WGS AF: 0.117 AC: 408 AN: 3478

ClinVar

Significance: Benign

Submissions summary: Benign:1

Revision: criteria provided, single submitter

Submissions by phenotype

not provided Benign:1

Nov 10, 2018

GeneDx

Significance: Benign

Review Status: criteria provided, single submitter

Collection Method: clinical testing

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Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.80
CADD	Benign	11
DANN	Benign	0.77
PhyloP100		0.98
Mutation Taster		=100/0	polymorphism (auto)

Splicing

Name	Calibrated prediction	Score	Prediction
SpliceAI score (max)		0.030		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: rs2236534; hg19: chr10-44874309;