Genetic Variant CHST15:c.-513+3560A>G (chr10-124089909-T-C) – ACMG Classification: Benign (-12 pts)

Variant summary

Our verdict is Benign. The variant received -12 ACMG points: 0P and 12B. BP4_StrongBA1

The NM_001270764.2(CHST15):c.-513+3560A>G variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.663 in 152,114 control chromosomes in the GnomAD database, including 33,660 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 0.66 ( 33660 hom., cov: 32)

Consequence

CHST15
NM_001270764.2 intron

Scores

Clinical Significance

Not reported in ClinVar

Conservation

PhyloP100: -0.513

Publications

3 publications found

Variant links:

Genes affected

CHST15 (HGNC:18137): (carbohydrate sulfotransferase 15) Chondroitin sulfate (CS) is a glycosaminoglycan which is an important structural component of the extracellular matrix and which links to proteins to form proteoglycans. Chondroitin sulfate E (CS-E) is an isomer of chondroitin sulfate in which the C-4 and C-6 hydroxyl groups are sulfated. This gene encodes a type II transmembrane glycoprotein that acts as a sulfotransferase to transfer sulfate to the C-6 hydroxal group of chondroitin sulfate. This gene has also been identified as being co-expressed with RAG1 in B-cells and as potentially acting as a B-cell surface signaling receptor. Alternative splicing results in multiple transcript variants encoding distinct isoforms. [provided by RefSeq, Jul 2012]

CHST15 links:

ENSG00000307215 (HGNC:):

ENSG00000307215 links:

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ACMG classification

Classification was made for transcript

Our verdict: Benign. The variant received -12 ACMG points.

BP4

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

BA1

GnomAd4 highest subpopulation (NFE) allele frequency at 95% confidence interval = 0.685 is higher than 0.05.

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_001270764.2. You can select a different transcript below to see updated ACMG assignments.

RefSeq Transcripts

Gene	Transcript	Tags	HGVSc	Effect	Exon Rank	Protein	UniProt
CHST15	NM_001270764.2	MANE Select	c.-513+3560A>G	intron	N/A	NP_001257693.1	Q7LFX5-1
CHST15	NM_015892.5		c.-513+2415A>G	intron	N/A	NP_056976.2
CHST15	NM_001270765.2		c.-513+3560A>G	intron	N/A	NP_001257694.1	Q7LFX5-2

Ensembl Transcripts

Gene	Transcript	Tags	HGVSc	Effect	Exon Rank	Protein	UniProt
CHST15	ENST00000435907.6	TSL:1 MANE Select	c.-513+3560A>G	intron	N/A	ENSP00000402394.1	Q7LFX5-1
CHST15	ENST00000346248.7	TSL:1	c.-513+2415A>G	intron	N/A	ENSP00000333947.6	Q7LFX5-1
CHST15	ENST00000874549.1		c.-513+2318A>G	intron	N/A	ENSP00000544608.1

Frequencies

GnomAD3 genomes

AF:

0.663

AC:

100807

AN:

151996

Hom.:

33628

Cov.:

show subpopulations

Gnomad AFR

AF:

0.663

Gnomad AMI

AF:

0.615

Gnomad AMR

AF:

0.635

Gnomad ASJ

AF:

0.542

Gnomad EAS

AF:

0.630

Gnomad SAS

AF:

0.681

Gnomad FIN

AF:

0.580

Gnomad MID

AF:

0.687

Gnomad NFE

AF:

0.690

Gnomad OTH

AF:

0.676

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

GnomAD4 genome

AF:

0.663

AC:

100886

AN:

152114

Hom.:

33660

Cov.:

AF XY:

0.657

AC XY:

48861

AN XY:

74362

show subpopulations

African (AFR)

AF:

0.663

AC:

27509

AN:

41504

American (AMR)

AF:

0.635

AC:

9697

AN:

15280

Ashkenazi Jewish (ASJ)

AF:

0.542

AC:

1881

AN:

3472

East Asian (EAS)

AF:

0.630

AC:

3248

AN:

5154

South Asian (SAS)

AF:

0.680

AC:

3283

AN:

4826

European-Finnish (FIN)

AF:

0.580

AC:

6131

AN:

10572

Middle Eastern (MID)

AF:

0.694

AC:

204

AN:

294

European-Non Finnish (NFE)

AF:

0.690

AC:

46938

AN:

67990

Other (OTH)

AF:

0.679

AC:

1435

AN:

2112

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.502

Heterozygous variant carriers

1744

3488

5231

6975

8719

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Genome Het

Genome Hom

Variant carriers

808

1616

2424

3232

4040

<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:

0.680

Hom.:

131823

Bravo

AF:

0.665

Asia WGS

AF:

0.638

AC:

2216

AN:

3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name

Calibrated prediction

Score

Prediction

BayesDel_noAF

Benign

-0.86

CADD

Benign

0.54

(source)

DANN

Benign

0.77

PhyloP100

-0.51

Mutation Taster

=100/0

polymorphism (auto)

(source)

Splicing

Name

Calibrated prediction

Score

Prediction

SpliceAI score (max)

0.0

Details are displayed if max score is > 0.2

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