rs2839695

Variant names:

• chr10-44378401-A-G
• rs2839695
• NM_199168.4:c.*232T>C

Variant summary

Our verdict is Benign. The variant received -20 ACMG points: 0P and 20B. BP4_Strong BP6_Very_Strong BA1

The ENST00000343575.11(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 ENST00000343575.11 3_prime_UTR
• Clinical Significance: Benign criteria provided, multiple submitters, no conflicts B:2
• Conservation: PhyloP100: -0.0830
• Publications: 16 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 -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 VariationId 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.

Variant Effect in Transcripts

ACMG analysis was done for transcript: ENST00000343575.11. 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.*232T>C		3_prime_UTR	Exon 3 of 3	NP_954637.1
	CXCL12	NM_001178134.2		c.266+236T>C		intron	N/A	NP_001171605.1
	CXCL12	NM_001033886.2		c.266+236T>C		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.*232T>C		3_prime_UTR	Exon 3 of 3	ENSP00000339913.6
	CXCL12	ENST00000395794.2	TSL:1	c.266+236T>C		intron	N/A	ENSP00000379140.2
	CXCL12	ENST00000374426.6	TSL:1	c.266+236T>C		intron	N/A	ENSP00000363548.2

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

African (AFR) AF: 0.194 AC: 6316 AN: 32504

American (AMR) AF: 0.0968 AC: 4022 AN: 41546

Ashkenazi Jewish (ASJ) AF: 0.189 AC: 4662 AN: 24670

East Asian (EAS) AF: 0.000223 AC: 8 AN: 35934

South Asian (SAS) AF: 0.0620 AC: 5185 AN: 83642

European-Finnish (FIN) AF: 0.221 AC: 7540 AN: 34188

Middle Eastern (MID) AF: 0.141 AC: 782 AN: 5540

European-Non Finnish (NFE) AF: 0.208 AC: 225307 AN: 1080618

Other (OTH) AF: 0.179 AC: 10301 AN: 57426

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

African (AFR) AF: 0.192 AC: 7986 AN: 41520

American (AMR) AF: 0.142 AC: 2179 AN: 15294

Ashkenazi Jewish (ASJ) AF: 0.185 AC: 640 AN: 3466

East Asian (EAS) AF: 0.00174 AC: 9 AN: 5184

South Asian (SAS) AF: 0.0535 AC: 258 AN: 4824

European-Finnish (FIN) AF: 0.214 AC: 2263 AN: 10584

Middle Eastern (MID) AF: 0.119 AC: 35 AN: 294

European-Non Finnish (NFE) AF: 0.209 AC: 14204 AN: 68002

Other (OTH) AF: 0.174 AC: 368 AN: 2116

Alfa AF: 0.195 Hom.: 8433

Bravo AF: 0.180

Asia WGS AF: 0.0430 AC: 151 AN: 3478

ClinVar

ClinVar submissions as Germline

Significance: Benign

Revision: criteria provided, multiple submitters, no conflicts

Pathogenic	VUS	Benign	Condition
-	-	2	not provided (2)

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.81
CADD	Benign	8.0
DANN	Benign	0.71
PhyloP100		-0.083
Mutation Taster		=100/0	polymorphism (auto)

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

Other links and lift over

dbSNP: rs2839695; hg19: chr10-44873849;