rs266092

Variant names:

• chr10-44370827-T-A
• rs266092
• ENST00000374429.6:c.*2501A>T

Variant summary

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

The ENST00000374429.6(CXCL12):​c.*2501A>T variant causes a 3 prime UTR change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0395 in 152,440 control chromosomes in the GnomAD database, including 152 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 0.039 (152 hom., cov: 33)
  • Exomes 𝑓: 0.057 (0 hom.)
• Consequence: CXCL12 ENST00000374429.6 3_prime_UTR
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 1.86
• Publications: 7 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=-0.62).
• BA1: GnomAd4 highest subpopulation (SAS) allele frequency at 95% confidence interval = 0.0913 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
CXCL12	NM_001277990.2	c.*2061A>T		3_prime_UTR_variant	Exon 3 of 3		NP_001264919.1
CXCL12	NM_000609.7	c.*2501A>T		3_prime_UTR_variant	Exon 4 of 4		NP_000600.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
CXCL12	ENST00000374429.6	c.*2501A>T		3_prime_UTR_variant	Exon 4 of 4	1		ENSP00000363551.2

Frequencies

GnomAD3 genomes AF: 0.0395 AC: 6006 AN: 152200 Hom.: 154 Cov.: 33

Gnomad AFR AF: 0.0220

Gnomad AMI AF: 0.0384

Gnomad AMR AF: 0.0303

Gnomad ASJ AF: 0.0795

Gnomad EAS AF: 0.00135

Gnomad SAS AF: 0.0981

Gnomad FIN AF: 0.0386

Gnomad MID AF: 0.0854

Gnomad NFE AF: 0.0489

Gnomad OTH AF: 0.0359

GnomAD4 exome AF: 0.0574 AC: 7 AN: 122 Hom.: 0 Cov.: 0 AF XY: 0.0510 AC XY: 5 AN XY: 98

African (AFR) AF: 0.00 AC: 0 AN: 2

American (AMR) AC: 0 AN: 0

Ashkenazi Jewish (ASJ) AC: 0 AN: 0

East Asian (EAS) AF: 0.00 AC: 0 AN: 6

South Asian (SAS) AF: 0.00 AC: 0 AN: 2

European-Finnish (FIN) AF: 0.125 AC: 1 AN: 8

Middle Eastern (MID) AC: 0 AN: 0

European-Non Finnish (NFE) AF: 0.0588 AC: 6 AN: 102

Other (OTH) AF: 0.00 AC: 0 AN: 2

GnomAD4 genome AF: 0.0394 AC: 6007 AN: 152318 Hom.: 152 Cov.: 33 AF XY: 0.0395 AC XY: 2945 AN XY: 74476

African (AFR) AF: 0.0221 AC: 918 AN: 41574

American (AMR) AF: 0.0302 AC: 462 AN: 15306

Ashkenazi Jewish (ASJ) AF: 0.0795 AC: 276 AN: 3470

East Asian (EAS) AF: 0.00135 AC: 7 AN: 5184

South Asian (SAS) AF: 0.0986 AC: 476 AN: 4828

European-Finnish (FIN) AF: 0.0386 AC: 410 AN: 10614

Middle Eastern (MID) AF: 0.0782 AC: 23 AN: 294

European-Non Finnish (NFE) AF: 0.0489 AC: 3325 AN: 68022

Other (OTH) AF: 0.0355 AC: 75 AN: 2114

Alfa AF: 0.0462 Hom.: 22

Bravo AF: 0.0346

Asia WGS AF: 0.0320 AC: 111 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.62
CADD	Benign	12
DANN	Benign	0.75
PhyloP100		1.9
Mutation Taster		=100/0	polymorphism (auto)

Splicing

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

Other links and lift over

dbSNP: rs266092; hg19: chr10-44866275;