rs4929827

Positions:

• chr10-124038144-A-T

Variant summary

Our verdict is Benign. Variant got -12 ACMG points: 0P and 12B. BP4_Strong BA1

The NM_001270764.2(CHST15):​c.1190+371T>A variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.2 in 149,730 control chromosomes in the GnomAD database, including 3,833 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 0.20 (3833 hom., cov: 29)
• Consequence: CHST15 NM_001270764.2 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.629

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]

ACMG classification

Verdict is Benign. Variant got -12 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-1.02).
• BA1: GnomAd4 highest subpopulation (NFE) allele frequency at 95% confidence interval = 0.276 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
CHST15	NM_001270764.2	c.1190+371T>A		intron_variant		ENST00000435907.6

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
CHST15	ENST00000435907.6	c.1190+371T>A		intron_variant		1	NM_001270764.2	P1
CHST15	ENST00000346248.7	c.1190+371T>A		intron_variant		1		P1
CHST15	ENST00000628426.1	c.1190+371T>A		intron_variant		2
CHST15	ENST00000476765.1	n.105+371T>A		intron_variant, non_coding_transcript_variant		3

Frequencies

GnomAD3 genomes AF: 0.200 AC: 29908 AN: 149614 Hom.: 3833 Cov.: 29

Gnomad AFR AF: 0.0704

Gnomad AMI AF: 0.389

Gnomad AMR AF: 0.204

Gnomad ASJ AF: 0.143

Gnomad EAS AF: 0.00829

Gnomad SAS AF: 0.0605

Gnomad FIN AF: 0.350

Gnomad MID AF: 0.114

Gnomad NFE AF: 0.280

Gnomad OTH AF: 0.209

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

GnomAD4 genome AF: 0.200 AC: 29900 AN: 149730 Hom.: 3833 Cov.: 29 AF XY: 0.200 AC XY: 14565 AN XY: 72896

Gnomad4 AFR AF: 0.0701

Gnomad4 AMR AF: 0.204

Gnomad4 ASJ AF: 0.143

Gnomad4 EAS AF: 0.00831

Gnomad4 SAS AF: 0.0606

Gnomad4 FIN AF: 0.350

Gnomad4 NFE AF: 0.280

Gnomad4 OTH AF: 0.207

Alfa AF: 0.241 Hom.: 643

Bravo AF: 0.185

Asia WGS AF: 0.0350 AC: 122 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-1.0
CADD	Benign	0.52
DANN	Benign	0.27
RBP_binding_hub_radar		0.0
RBP_regulation_power_radar		1.0

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

LitVar

Other links and lift over

dbSNP: rs4929827; hg19: chr10-125797660;