dbSNP rs140248633: CXCL12:c.*232A>G (chr10-44373096-T-C) – ACMG Classification: Benign (-7 pts)

Variant summary

Our verdict is Benign. The variant received -7 ACMG points: 0P and 7B. BP4_ModerateBP6BS2

The NM_001277990.2(CXCL12):c.110-6A>G variant causes a splice region, intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00294 in 1,536,422 control chromosomes in the GnomAD database, including 8 homozygotes. In-silico tool predicts a benign outcome for this variant. 2/2 splice prediction tools predict no significant impact on normal splicing. Variant has been reported in ClinVar as Likely benign (no stars).

Frequency

Genomes: 𝑓 0.0023 ( 1 hom., cov: 33)

Exomes 𝑓: 0.0030 ( 7 hom. )

Consequence

CXCL12
NM_001277990.2 splice_region, intron

Scores

Splicing: ADA: 0.00003135

Clinical Significance

Likely benign no assertion criteria provided B:1

Conservation

PhyloP100: -0.397

Publications

0 publications found

Variant links:

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]

CXCL12 links:

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ACMG classification

Classification was made for transcript

Our verdict: Benign. The variant received -7 ACMG points.

BP4

Computational evidence support a benign effect (BayesDel_noAF=-0.42).

BP6

Variant 10-44373096-T-C is Benign according to our data. Variant chr10-44373096-T-C is described in ClinVar as Likely_benign. ClinVar VariationId is 3037442.Status of the report is no_assertion_criteria_provided, 0 stars.

BS2

High Homozygotes in GnomAdExome4 at 7 gene

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_000609.7		c.*232A>G		3_prime_UTR	Exon 4 of 4	NP_000600.1	P48061-1
	CXCL12	NM_001277990.2		c.110-6A>G		splice_region intron	N/A	NP_001264919.1	P48061-7

Ensembl Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	CXCL12	ENST00000374429.6	TSL:1	c.*232A>G		3_prime_UTR	Exon 4 of 4	ENSP00000363551.2	P48061-1
	CXCL12	ENST00000395793.7	TSL:5	c.110-6A>G		splice_region intron	N/A	ENSP00000379139.3	P48061-7

Frequencies

GnomAD3 genomes

AF:

0.00235

AC:

358

AN:

152250

Hom.:

Cov.:

show subpopulations

Gnomad AFR

AF:

0.000868

Gnomad AMI

AF:

0.00

Gnomad AMR

AF:

0.00170

Gnomad ASJ

AF:

0.00230

Gnomad EAS

AF:

0.00

Gnomad SAS

AF:

0.000414

Gnomad FIN

AF:

0.000941

Gnomad MID

AF:

0.00

Gnomad NFE

AF:

0.00394

Gnomad OTH

AF:

0.00382

GnomAD2 exomes

AF:

0.00222

AC:

310

AN:

139700

AF XY:

0.00242

show subpopulations

Gnomad AFR exome

AF:

0.000427

Gnomad AMR exome

AF:

0.00144

Gnomad ASJ exome

AF:

0.000604

Gnomad EAS exome

AF:

0.00

Gnomad FIN exome

AF:

0.000616

Gnomad NFE exome

AF:

0.00410

Gnomad OTH exome

AF:

0.00337

GnomAD4 exome

AF:

0.00301

AC:

4161

AN:

1384054

Hom.:

Cov.:

AF XY:

0.00302

AC XY:

2065

AN XY:

682800

show subpopulations

African (AFR)

AF:

0.000349

AC:

AN:

31498

American (AMR)

AF:

0.00167

AC:

AN:

35412

Ashkenazi Jewish (ASJ)

AF:

0.000678

AC:

AN:

25082

East Asian (EAS)

AF:

0.0000280

AC:

AN:

35706

South Asian (SAS)

AF:

0.000835

AC:

AN:

79010

European-Finnish (FIN)

AF:

0.000587

AC:

AN:

35770

Middle Eastern (MID)

AF:

0.00369

AC:

AN:

5684

European-Non Finnish (NFE)

AF:

0.00355

AC:

3823

AN:

1078078

Other (OTH)

AF:

0.00246

AC:

142

AN:

57814

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.497

Heterozygous variant carriers

257

514

771

1028

1285

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Exome Het

Exome Hom

Variant carriers

130

260

390

520

650

<30

30-35

35-40

40-45

45-50

50-55

55-60

60-65

65-70

70-75

75-80

>80

Age

GnomAD4 genome

AF:

0.00235

AC:

358

AN:

152368

Hom.:

Cov.:

AF XY:

0.00203

AC XY:

151

AN XY:

74508

show subpopulations

African (AFR)

AF:

0.000866

AC:

AN:

41588

American (AMR)

AF:

0.00170

AC:

AN:

15310

Ashkenazi Jewish (ASJ)

AF:

0.00230

AC:

AN:

3472

East Asian (EAS)

AF:

0.00

AC:

AN:

5188

South Asian (SAS)

AF:

0.000414

AC:

AN:

4832

European-Finnish (FIN)

AF:

0.000941

AC:

AN:

10626

Middle Eastern (MID)

AF:

0.00

AC:

AN:

294

European-Non Finnish (NFE)

AF:

0.00394

AC:

268

AN:

68032

Other (OTH)

AF:

0.00378

AC:

AN:

2116

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.510

Heterozygous variant carriers

105

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Genome Het

Variant carriers

<30

30-35

35-40

40-45

45-50

50-55

55-60

60-65

65-70

70-75

75-80

>80

Age

Alfa

AF:

0.00277

Hom.:

Bravo

AF:

0.00232

Asia WGS

AF:

0.000289

AC:

AN:

3478

ClinVar

ClinVar submissions

Significance:Likely benign

Revision:no assertion criteria provided

View on ClinVar

Pathogenic

VUS

Benign

Condition

CXCL12-related disorder (1)

Computational scores

Source: dbNSFP v4.9

Name

Calibrated prediction

Score

Prediction

BayesDel_noAF

Benign

-0.42

CADD

Benign

9.1

(source)

DANN

Benign

0.75

PhyloP100

-0.40

Mutation Taster

=98/2

polymorphism

(source)

Splicing

Name

Calibrated prediction

Score

Prediction

dbscSNV1_ADA

Benign

0.000031

dbscSNV1_RF

Benign

0.012

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

Publications

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Variant summary

Frequency

Consequence

Scores

Clinical Significance

Conservation

Publications

ACMG classification

Variant Effect in Transcripts

RefSeq Transcripts

Ensembl Transcripts

Frequencies

Age Distribution

Age Distribution

ClinVar

Computational scores

Splicing

Publications

Other links and lift over