10-44382053-T-C

Variant names:

• chr10-44382053-T-C
• rs11592974
• NM_199168.4:c.62-1173A>G

Variant summary

Our verdict is Benign. The variant received -12 ACMG points: 0P and 12B. BP4_Strong BA1

The NM_199168.4(CXCL12):​c.62-1173A>G variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.156 in 152,138 control chromosomes in the GnomAD database, including 2,109 homozygotes. In-silico tool predicts a benign outcome for this variant. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar.

• Frequency: Genomes: 𝑓 0.16 (2109 hom., cov: 33)
• Consequence: CXCL12 NM_199168.4 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -2.12
• Publications: 2 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 -12 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.91).
• BA1: GnomAd4 highest subpopulation (NFE) allele frequency at 95% confidence interval = 0.203 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

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	CXCL12	NM_199168.4	MANE Select	c.62-1173A>G		intron	N/A	NP_954637.1	P48061-2
	CXCL12	NM_001178134.2		c.62-1173A>G		intron	N/A	NP_001171605.1	P48061-4
	CXCL12	NM_001033886.2		c.62-1173A>G		intron	N/A	NP_001029058.1	P48061-3

Ensembl Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	CXCL12	ENST00000343575.11	TSL:1 MANE Select	c.62-1173A>G		intron	N/A	ENSP00000339913.6	P48061-2
	CXCL12	ENST00000395794.2	TSL:1	c.62-1173A>G		intron	N/A	ENSP00000379140.2	P48061-4
	CXCL12	ENST00000374426.6	TSL:1	c.62-1173A>G		intron	N/A	ENSP00000363548.2	P48061-3

Frequencies

GnomAD3 genomes AF: 0.156 AC: 23679 AN: 152020 Hom.: 2108 Cov.: 33

Gnomad AFR AF: 0.0981

Gnomad AMI AF: 0.161

Gnomad AMR AF: 0.132

Gnomad ASJ AF: 0.164

Gnomad EAS AF: 0.00154

Gnomad SAS AF: 0.0524

Gnomad FIN AF: 0.215

Gnomad MID AF: 0.0828

Gnomad NFE AF: 0.206

Gnomad OTH AF: 0.152

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

GnomAD4 genome AF: 0.156 AC: 23681 AN: 152138 Hom.: 2109 Cov.: 33 AF XY: 0.153 AC XY: 11385 AN XY: 74372

African (AFR) AF: 0.0980 AC: 4071 AN: 41520

American (AMR) AF: 0.131 AC: 2008 AN: 15284

Ashkenazi Jewish (ASJ) AF: 0.164 AC: 567 AN: 3466

East Asian (EAS) AF: 0.00155 AC: 8 AN: 5172

South Asian (SAS) AF: 0.0517 AC: 249 AN: 4820

European-Finnish (FIN) AF: 0.215 AC: 2274 AN: 10576

Middle Eastern (MID) AF: 0.0890 AC: 26 AN: 292

European-Non Finnish (NFE) AF: 0.206 AC: 14013 AN: 67984

Other (OTH) AF: 0.151 AC: 318 AN: 2112

Alfa AF: 0.169 Hom.: 942

Bravo AF: 0.147

Asia WGS AF: 0.0350 AC: 124 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.91
CADD	Benign	0.23
DANN	Benign	0.45
PhyloP100		-2.1
Mutation Taster		=100/0	polymorphism (auto)

Splicing

Name	Calibrated prediction	Score	Prediction
SpliceAI score (max)		0.20		Details are displayed if max score is > 0.2
DS_AG_spliceai		0.20		Position offset: -35

Find out detailed SpliceAI scores and Pangolin per-transcript scores at spliceailookup.broadinstitute.org

Other links and lift over

dbSNP: rs11592974; hg19: chr10-44877501;