NM_199168.4:c.62-258A>T

Variant names:

• chr10-44381138-T-A
• rs10793538
• NM_199168.4:c.62-258A>T

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.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 NM_199168.4 intron
• Clinical Significance: Benign criteria provided, single submitter B:1
• Conservation: PhyloP100: 0.0970
• Publications: 6 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 10-44381138-T-A is Benign according to our data. Variant chr10-44381138-T-A is described in ClinVar as Benign. ClinVar VariationId 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.

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_199168.4. You can select a different transcript below to see updated ACMG assignments.

RefSeq Transcripts

Selected	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	CXCL12	NM_199168.4	MANE Select	c.62-258A>T		intron	N/A	NP_954637.1
	CXCL12	NM_001178134.2		c.62-258A>T		intron	N/A	NP_001171605.1
	CXCL12	NM_001033886.2		c.62-258A>T		intron	N/A	NP_001029058.1

Ensembl Transcripts

Selected	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	CXCL12	ENST00000343575.11	TSL:1 MANE Select	c.62-258A>T		intron	N/A	ENSP00000339913.6
	CXCL12	ENST00000395794.2	TSL:1	c.62-258A>T		intron	N/A	ENSP00000379140.2
	CXCL12	ENST00000374426.6	TSL:1	c.62-258A>T		intron	N/A	ENSP00000363548.2

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

African (AFR) AF: 0.760 AC: 31428 AN: 41354

American (AMR) AF: 0.946 AC: 14473 AN: 15292

Ashkenazi Jewish (ASJ) AF: 0.985 AC: 3419 AN: 3470

East Asian (EAS) AF: 0.944 AC: 4866 AN: 5156

South Asian (SAS) AF: 0.938 AC: 4514 AN: 4810

European-Finnish (FIN) AF: 0.980 AC: 10381 AN: 10596

Middle Eastern (MID) AF: 0.959 AC: 280 AN: 292

European-Non Finnish (NFE) AF: 0.966 AC: 65662 AN: 67970

Other (OTH) AF: 0.934 AC: 1969 AN: 2108

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

Nov 11, 2018

GeneDx

Significance: Benign

Review Status: criteria provided, single submitter

Collection Method: clinical testing

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.80
CADD	Benign	3.1
DANN	Benign	0.86
PhyloP100		0.097
Mutation Taster		=100/0	polymorphism (auto)

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

Other links and lift over

dbSNP: rs10793538; hg19: chr10-44876586;