rs10793538

Positions:

• chr10-44381138-T-A
• chr10-44381138-T-C
• chr10-44381138-T-G

Variant summary

Our verdict is Benign. Variant got -14 ACMG points: 0P and 14B. BP4_Strong BP6_Moderate BA1

The ENST00000343575.11(CXCL12):​c.62-258A>T variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.907 in 151,960 control chromosomes in the GnomAD database, including 63,091 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★).

• Frequency: Genomes: 𝑓 0.91 (63091 hom., cov: 32)
• Consequence: CXCL12 ENST00000343575.11 intron
• Clinical Significance: Benign criteria provided, single submitter B:1
• Conservation: PhyloP100: 0.0970

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 -14 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.8).
• BP6: Variant 10-44381138-T-A is Benign according to our data. Variant chr10-44381138-T-A is described in ClinVar as [Benign]. Clinvar id is 1181019.Status of the report is criteria_provided_single_submitter, 1 stars.
• BA1: GnomAd4 highest subpopulation (NFE) allele frequency at 95% confidence interval = 0.96 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
CXCL12	NM_199168.4	c.62-258A>T		intron_variant		ENST00000343575.11	NP_954637.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
CXCL12	ENST00000343575.11	c.62-258A>T		intron_variant		1	NM_199168.4	ENSP00000339913	P4

Frequencies

GnomAD3 genomes AF: 0.907 AC: 137745 AN: 151842 Hom.: 63054 Cov.: 32

Gnomad AFR AF: 0.760

Gnomad AMI AF: 0.931

Gnomad AMR AF: 0.947

Gnomad ASJ AF: 0.985

Gnomad EAS AF: 0.943

Gnomad SAS AF: 0.939

Gnomad FIN AF: 0.980

Gnomad MID AF: 0.965

Gnomad NFE AF: 0.966

Gnomad OTH AF: 0.933

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

GnomAD4 genome AF: 0.907 AC: 137841 AN: 151960 Hom.: 63091 Cov.: 32 AF XY: 0.910 AC XY: 67572 AN XY: 74274

Gnomad4 AFR AF: 0.760

Gnomad4 AMR AF: 0.946

Gnomad4 ASJ AF: 0.985

Gnomad4 EAS AF: 0.944

Gnomad4 SAS AF: 0.938

Gnomad4 FIN AF: 0.980

Gnomad4 NFE AF: 0.966

Gnomad4 OTH AF: 0.934

Alfa AF: 0.933 Hom.: 7762

Bravo AF: 0.898

Asia WGS AF: 0.930 AC: 3235 AN: 3478

ClinVar

Significance: Benign

Submissions summary: Benign:1

Revision: criteria provided, single submitter

Submissions by phenotype

not provided Benign:1

Benign, criteria provided, single submitter

clinical testing

GeneDx

Nov 11, 2018

- -

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.80
CADD	Benign	3.1
DANN	Benign	0.86

Splicing

Name	Calibrated prediction	Score	Prediction
SpliceAI score (max)		0.020		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: rs10793538; hg19: chr10-44876586;