10-124089909-T-C

Variant names:

• chr10-124089909-T-C
• rs4397783
• NM_001270764.2:c.-513+3560A>G

Variant summary

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

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
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.513
• Publications: 3 publications found

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]

ENSG00000307215 (HGNC:):

ACMG classification

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.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
CHST15	NM_001270764.2	c.-513+3560A>G		intron_variant	Intron 1 of 7	ENST00000435907.6	NP_001257693.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
CHST15	ENST00000435907.6	c.-513+3560A>G		intron_variant	Intron 1 of 7	1	NM_001270764.2	ENSP00000402394.1

Frequencies

GnomAD3 genomes AF: 0.663 AC: 100807 AN: 151996 Hom.: 33628 Cov.: 32

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.: 32 AF XY: 0.657 AC XY: 48861 AN XY: 74362

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

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 v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.86
CADD	Benign	0.54
DANN	Benign	0.77
PhyloP100		-0.51
Mutation Taster		=100/0	polymorphism (auto)

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

Other links and lift over

dbSNP: rs4397783; hg19: chr10-125849425;