10-44385008-CGCGGGCGGGCGGGCGG-CGCGGGCGGGCGG

Variant names:

• chr10-44385008-CGCGG-C
• rs76444314
• NM_199168.4:c.-7_-4delCCGC

Variant summary

Our verdict is Benign. The variant received -9 ACMG points: 0P and 9B. BP6 BA1

The NM_199168.4(CXCL12):​c.-7_-4delCCGC variant causes a 5 prime UTR change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0243 in 387,690 control chromosomes in the GnomAD database, including 289 homozygotes. Variant has been reported in ClinVar as Benign (no stars).

• Frequency:
  • Genomes: 𝑓 0.035 (185 hom., cov: 0)
  • Exomes 𝑓: 0.020 (104 hom.)
• Consequence: CXCL12 NM_199168.4 5_prime_UTR
• Clinical Significance: Benign no assertion criteria provided B:1
• Conservation: PhyloP100: 0.689
• Publications: 0 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 -9 ACMG points.

• BP6: Variant 10-44385008-CGCGG-C is Benign according to our data. Variant chr10-44385008-CGCGG-C is described in ClinVar as Benign. ClinVar VariationId is 3056613.Status of the report is no_assertion_criteria_provided, 0 stars.
• BA1: GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.111 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
CXCL12	NM_199168.4	c.-7_-4delCCGC		5_prime_UTR_variant	Exon 1 of 3	ENST00000343575.11	NP_954637.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
CXCL12	ENST00000343575.11	c.-7_-4delCCGC		5_prime_UTR_variant	Exon 1 of 3	1	NM_199168.4	ENSP00000339913.6

Frequencies

GnomAD3 genomes AF: 0.0350 AC: 4186 AN: 119490 Hom.: 185 Cov.: 0

Gnomad AFR AF: 0.114

Gnomad AMI AF: 0.00131

Gnomad AMR AF: 0.0168

Gnomad ASJ AF: 0.0226

Gnomad EAS AF: 0.000293

Gnomad SAS AF: 0.000652

Gnomad FIN AF: 0.00

Gnomad MID AF: 0.0257

Gnomad NFE AF: 0.00222

Gnomad OTH AF: 0.0289

GnomAD2 exomes AF: 0.00959 AC: 548 AN: 57116 AF XY: 0.00824

Gnomad AFR exome AF: 0.0857

Gnomad AMR exome AF: 0.0186

Gnomad ASJ exome AF: 0.0265

Gnomad EAS exome AF: 0.00644

Gnomad FIN exome AF: 0.00438

Gnomad NFE exome AF: 0.00414

Gnomad OTH exome AF: 0.0173

GnomAD4 exome AF: 0.0195 AC: 5238 AN: 268168 Hom.: 104 AF XY: 0.0169 AC XY: 2485 AN XY: 146636

African (AFR) AF: 0.240 AC: 1753 AN: 7314

American (AMR) AF: 0.0217 AC: 281 AN: 12920

Ashkenazi Jewish (ASJ) AF: 0.0488 AC: 404 AN: 8280

East Asian (EAS) AF: 0.0162 AC: 36 AN: 2222

South Asian (SAS) AF: 0.00464 AC: 179 AN: 38568

European-Finnish (FIN) AF: 0.00640 AC: 53 AN: 8276

Middle Eastern (MID) AF: 0.0615 AC: 62 AN: 1008

European-Non Finnish (NFE) AF: 0.0114 AC: 2026 AN: 178072

Other (OTH) AF: 0.0386 AC: 444 AN: 11508

GnomAD4 genome AF: 0.0351 AC: 4192 AN: 119522 Hom.: 185 Cov.: 0 AF XY: 0.0345 AC XY: 1973 AN XY: 57150

African (AFR) AF: 0.114 AC: 3745 AN: 32864

American (AMR) AF: 0.0167 AC: 192 AN: 11466

Ashkenazi Jewish (ASJ) AF: 0.0226 AC: 70 AN: 3100

East Asian (EAS) AF: 0.000293 AC: 1 AN: 3408

South Asian (SAS) AF: 0.000652 AC: 2 AN: 3066

European-Finnish (FIN) AF: 0.00 AC: 0 AN: 5414

Middle Eastern (MID) AF: 0.0285 AC: 7 AN: 246

European-Non Finnish (NFE) AF: 0.00221 AC: 127 AN: 57556

Other (OTH) AF: 0.0287 AC: 47 AN: 1640

Alfa AF: 0.000113 Hom.: 0

ClinVar

Significance: Benign

Submissions summary: Benign:1

Revision: no assertion criteria provided

Submissions by phenotype

CXCL12-related disorder Benign:1

Jan 06, 2020

PreventionGenetics, part of Exact Sciences

Significance: Benign

Review Status: no assertion criteria provided

Collection Method: clinical testing

This variant is classified as benign based on ACMG/AMP sequence variant interpretation guidelines (Richards et al. 2015 PMID: 25741868, with internal and published modifications). -

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
PhyloP100		0.69
Mutation Taster		=299/1	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: rs76444314; hg19: chr10-44880456; COSMIC: COSV59108147;