rs266090

Variant names:

• chr10-44373416-C-T
• rs266090
• ENST00000374429.6:c.267-73G>A

Your query was ambiguous. Multiple possible variants found:

• chr10-44373416-C-T
• chr10-44373416-C-A

Variant summary

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

The NM_001277990.2(CXCL12):​c.110-326G>A variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0466 in 1,349,348 control chromosomes in the GnomAD database, including 1,820 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★★).

• Frequency:
  • Genomes: 𝑓 0.039 (149 hom., cov: 34)
  • Exomes 𝑓: 0.048 (1671 hom.)
• Consequence: CXCL12 NM_001277990.2 intron
• Clinical Significance: Benign criteria provided, multiple submitters, no conflicts B:2
• Conservation: PhyloP100: -2.63
• Publications: 4 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=-0.92).
• BP6: Variant 10-44373416-C-T is Benign according to our data. Variant chr10-44373416-C-T is described in ClinVar as Benign. ClinVar VariationId is 1237787.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars.
• BA1: GnomAd4 highest subpopulation (SAS) allele frequency at 95% confidence interval = 0.0914 is higher than 0.05.

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_001277990.2. 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_001277990.2		c.110-326G>A		intron	N/A	NP_001264919.1	P48061-7
	CXCL12	NM_000609.7		c.267-73G>A		intron	N/A	NP_000600.1	P48061-1

Ensembl Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	CXCL12	ENST00000374429.6	TSL:1	c.267-73G>A		intron	N/A	ENSP00000363551.2	P48061-1
	CXCL12	ENST00000395793.7	TSL:5	c.110-326G>A		intron	N/A	ENSP00000379139.3	P48061-7

Frequencies

GnomAD3 genomes AF: 0.0390 AC: 5932 AN: 152190 Hom.: 151 Cov.: 34

Gnomad AFR AF: 0.0220

Gnomad AMI AF: 0.0384

Gnomad AMR AF: 0.0296

Gnomad ASJ AF: 0.0795

Gnomad EAS AF: 0.00136

Gnomad SAS AF: 0.0983

Gnomad FIN AF: 0.0386

Gnomad MID AF: 0.0854

Gnomad NFE AF: 0.0480

Gnomad OTH AF: 0.0349

GnomAD4 exome AF: 0.0476 AC: 56944 AN: 1197040 Hom.: 1671 AF XY: 0.0502 AC XY: 30263 AN XY: 602506

African (AFR) AF: 0.0222 AC: 617 AN: 27748

American (AMR) AF: 0.0221 AC: 834 AN: 37812

Ashkenazi Jewish (ASJ) AF: 0.0807 AC: 1928 AN: 23900

East Asian (EAS) AF: 0.000250 AC: 9 AN: 36018

South Asian (SAS) AF: 0.105 AC: 7955 AN: 76100

European-Finnish (FIN) AF: 0.0365 AC: 1841 AN: 50378

Middle Eastern (MID) AF: 0.0857 AC: 456 AN: 5318

European-Non Finnish (NFE) AF: 0.0460 AC: 40882 AN: 888412

Other (OTH) AF: 0.0472 AC: 2422 AN: 51354

GnomAD4 genome AF: 0.0390 AC: 5933 AN: 152308 Hom.: 149 Cov.: 34 AF XY: 0.0390 AC XY: 2907 AN XY: 74468

African (AFR) AF: 0.0220 AC: 917 AN: 41592

American (AMR) AF: 0.0295 AC: 451 AN: 15308

Ashkenazi Jewish (ASJ) AF: 0.0795 AC: 276 AN: 3472

East Asian (EAS) AF: 0.00136 AC: 7 AN: 5154

South Asian (SAS) AF: 0.0988 AC: 476 AN: 4820

European-Finnish (FIN) AF: 0.0386 AC: 410 AN: 10624

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

European-Non Finnish (NFE) AF: 0.0480 AC: 3265 AN: 68018

Other (OTH) AF: 0.0345 AC: 73 AN: 2114

Alfa AF: 0.0444 Hom.: 17

Bravo AF: 0.0341

Asia WGS AF: 0.0310 AC: 110 AN: 3478

ClinVar

ClinVar submissions

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	-0.92
CADD	Benign	0.044
DANN	Benign	0.58
PhyloP100		-2.6
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: rs266090; hg19: chr10-44868864;