Genetic Variant ENST00000374429.6:c.267-235G>A (chr10-44373578-C-T) – ACMG Classification: Benign (-14 pts)

Variant summary

Our verdict is Benign. The variant received -14 ACMG points: 0P and 14B. BP4_StrongBP6_ModerateBA1

The ENST00000374429.6(CXCL12):c.267-235G>A variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.193 in 152,202 control chromosomes in the GnomAD database, including 3,240 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★).

Frequency

Genomes: 𝑓 0.19 ( 3240 hom., cov: 33)

Consequence

CXCL12
ENST00000374429.6 intron

Scores

Clinical Significance

Benign criteria provided, single submitter B:1

Conservation

PhyloP100: -0.785

Publications

2 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 -14 ACMG points.

BP4

Computational evidence support a benign effect (BayesDel_noAF=-0.86).

BP6

Variant 10-44373578-C-T is Benign according to our data. Variant chr10-44373578-C-T is described in ClinVar as Benign. ClinVar VariationId is 1272932.Status of the report is criteria_provided_single_submitter, 1 stars.

BA1

GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.423 is higher than 0.05.

Variant Effect in Transcripts

ACMG analysis was done for transcript: ENST00000374429.6. 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.110-488G>A		intron	N/A	NP_001264919.1	P48061-7
	CXCL12	NM_000609.7		c.267-235G>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.267-235G>A		intron	N/A	ENSP00000363551.2	P48061-1
	CXCL12	ENST00000395793.7	TSL:5	c.110-488G>A		intron	N/A	ENSP00000379139.3	P48061-7

Frequencies

GnomAD3 genomes

AF:

0.193

AC:

29319

AN:

152082

Hom.:

3229

Cov.:

show subpopulations

Gnomad AFR

AF:

0.109

Gnomad AMI

AF:

0.222

Gnomad AMR

AF:

0.199

Gnomad ASJ

AF:

0.249

Gnomad EAS

AF:

0.438

Gnomad SAS

AF:

0.275

Gnomad FIN

AF:

0.203

Gnomad MID

AF:

0.334

Gnomad NFE

AF:

0.211

Gnomad OTH

AF:

0.220

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

GnomAD4 genome

AF:

0.193

AC:

29344

AN:

152202

Hom.:

3240

Cov.:

AF XY:

0.195

AC XY:

14538

AN XY:

74412

show subpopulations

African (AFR)

AF:

0.109

AC:

4544

AN:

41548

American (AMR)

AF:

0.199

AC:

3046

AN:

15304

Ashkenazi Jewish (ASJ)

AF:

0.249

AC:

866

AN:

3472

East Asian (EAS)

AF:

0.438

AC:

2263

AN:

5162

South Asian (SAS)

AF:

0.274

AC:

1324

AN:

4824

European-Finnish (FIN)

AF:

0.203

AC:

2152

AN:

10592

Middle Eastern (MID)

AF:

0.329

AC:

AN:

292

European-Non Finnish (NFE)

AF:

0.211

AC:

14368

AN:

67982

Other (OTH)

AF:

0.228

AC:

483

AN:

2116

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.499

Heterozygous variant carriers

1234

2468

3702

4936

6170

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Genome Het

Genome Hom

Variant carriers

324

648

972

1296

1620

<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:

0.123

Hom.:

264

Bravo

AF:

0.187

Asia WGS

AF:

0.360

AC:

1250

AN:

3478

ClinVar

ClinVar submissions

Significance:Benign

Revision:criteria provided, single submitter

View on ClinVar

Pathogenic

VUS

Benign

Condition

not provided (1)

Computational scores

Source: dbNSFP v4.9

Name

Calibrated prediction

Score

Prediction

BayesDel_noAF

Benign

-0.86

CADD

Benign

1.0

(source)

DANN

Benign

0.72

PhyloP100

-0.79

Mutation Taster

=100/0

polymorphism (auto)

(source)

Splicing

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

ClinVar

Computational scores

Splicing

Publications

Other links and lift over