rs2839695

Positions:

• chr10-44378401-A-G

Variant summary

Our verdict is Benign. Variant got -20 ACMG points: 0P and 20B. BP4_Strong BP6_Very_Strong BA1

The NM_199168.4(CXCL12):​c.*232T>C variant causes a 3 prime UTR change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.189 in 1,548,262 control chromosomes in the GnomAD database, including 29,792 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★★).

• Frequency:
  • Genomes: 𝑓 0.18 (2729 hom., cov: 32)
  • Exomes 𝑓: 0.19 (27063 hom.)
• Consequence: CXCL12 NM_199168.4 3_prime_UTR
• Clinical Significance: Benign criteria provided, multiple submitters, no conflicts B:2
• Conservation: PhyloP100: -0.0830

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

Verdict is Benign. Variant got -20 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.81).
• BP6: Variant 10-44378401-A-G is Benign according to our data. Variant chr10-44378401-A-G is described in ClinVar as [Benign]. Clinvar id is 1251315.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars.
• BA1: GnomAd4 highest subpopulation (NFE) allele frequency at 95% confidence interval = 0.206 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
CXCL12	NM_199168.4	c.*232T>C		3_prime_UTR_variant	3/3	ENST00000343575.11	NP_954637.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
CXCL12	ENST00000343575.11	c.*232T>C		3_prime_UTR_variant	3/3	1	NM_199168.4	ENSP00000339913.6

Frequencies

GnomAD3 genomes AF: 0.185 AC: 28082 AN: 152076 Hom.: 2727 Cov.: 32

Gnomad AFR AF: 0.192

Gnomad AMI AF: 0.164

Gnomad AMR AF: 0.143

Gnomad ASJ AF: 0.185

Gnomad EAS AF: 0.00173

Gnomad SAS AF: 0.0541

Gnomad FIN AF: 0.214

Gnomad MID AF: 0.111

Gnomad NFE AF: 0.209

Gnomad OTH AF: 0.176

GnomAD4 exome AF: 0.189 AC: 264123 AN: 1396068 Hom.: 27063 Cov.: 34 AF XY: 0.185 AC XY: 128554 AN XY: 693114

Gnomad4 AFR exome AF: 0.194

Gnomad4 AMR exome AF: 0.0968

Gnomad4 ASJ exome AF: 0.189

Gnomad4 EAS exome AF: 0.000223

Gnomad4 SAS exome AF: 0.0620

Gnomad4 FIN exome AF: 0.221

Gnomad4 NFE exome AF: 0.208

Gnomad4 OTH exome AF: 0.179

GnomAD4 genome AF: 0.185 AC: 28091 AN: 152194 Hom.: 2729 Cov.: 32 AF XY: 0.181 AC XY: 13438 AN XY: 74402

Gnomad4 AFR AF: 0.192

Gnomad4 AMR AF: 0.142

Gnomad4 ASJ AF: 0.185

Gnomad4 EAS AF: 0.00174

Gnomad4 SAS AF: 0.0535

Gnomad4 FIN AF: 0.214

Gnomad4 NFE AF: 0.209

Gnomad4 OTH AF: 0.174

Alfa AF: 0.195 Hom.: 5080

Bravo AF: 0.180

Asia WGS AF: 0.0430 AC: 151 AN: 3478

ClinVar

Significance: Benign

Submissions summary: Benign:2

Revision: criteria provided, multiple submitters, no conflicts

Submissions by phenotype

not provided Benign:2

Benign, criteria provided, single submitter	clinical testing	GeneDx	Jun 18, 2021	- -
Benign, criteria provided, single submitter	not provided	Breakthrough Genomics, Breakthrough Genomics	-	- -

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.81
CADD	Benign	8.0
DANN	Benign	0.71

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

Publications

LitVar

Other links and lift over

dbSNP: rs2839695; hg19: chr10-44873849;