10-124021236-CG-C

Position:

• chr10-124021236-CG-C

Variant summary

Our verdict is Likely benign. Variant got -2 ACMG points: 0P and 2B. BP6_Moderate

The NM_014863.4(CHST15):​c.1366delC​(p.Arg456fs) variant causes a frameshift change involving the alteration of a non-conserved nucleotide. Variant has been reported in ClinVar as Benign (★).

• Frequency:
  • Genomes: 𝑓 0.61 (13473 hom., cov: 0)
  • Exomes 𝑓: 0.54 (115795 hom.)
  • Failed GnomAD Quality Control
• Consequence: CHST15 NM_014863.4 frameshift
• Clinical Significance: Benign criteria provided, single submitter B:1
• Conservation: PhyloP100: -0.619

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 (HGNC:):

ACMG classification

Verdict is Likely_benign. Variant got -2 ACMG points.

• BP6: Variant 10-124021236-CG-C is Benign according to our data. Variant chr10-124021236-CG-C is described in ClinVar as [Benign]. Clinvar id is 1262272.Status of the report is criteria_provided_single_submitter, 1 stars. Variant chr10-124021236-CG-C is described in Lovd as [Benign].

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
CHST15	NM_001270764.2	c.1347+19delC		intron_variant		ENST00000435907.6	NP_001257693.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
CHST15	ENST00000435907.6	c.1347+19delC		intron_variant		1	NM_001270764.2	ENSP00000402394.1
CHST15	ENST00000346248.7	c.1347+19delC		intron_variant		1		ENSP00000333947.6
CHST15	ENST00000628426.1	c.1366delC	p.Arg456fs	frameshift_variant	6/6	2		ENSP00000485905.1
CHST15	ENST00000476765.1	n.281delC		non_coding_transcript_exon_variant	2/2	3

Frequencies

GnomAD3 genomes AF: 0.00 AC: 56075 AN: 91708 Hom.: 13457 Cov.: 0 FAILED QC

Gnomad AFR AF: 0.592

Gnomad AMI AF: 0.638

Gnomad AMR AF: 0.674

Gnomad ASJ AF: 0.589

Gnomad EAS AF: 0.677

Gnomad SAS AF: 0.609

Gnomad FIN AF: 0.650

Gnomad MID AF: 0.670

Gnomad NFE AF: 0.600

Gnomad OTH AF: 0.644

GnomAD3 exomes AF: 0.570 AC: 78279 AN: 137330 Hom.: 17178 AF XY: 0.566 AC XY: 42312 AN XY: 74782

Gnomad AFR exome AF: 0.552

Gnomad AMR exome AF: 0.619

Gnomad ASJ exome AF: 0.512

Gnomad EAS exome AF: 0.662

Gnomad SAS exome AF: 0.531

Gnomad FIN exome AF: 0.573

Gnomad NFE exome AF: 0.553

Gnomad OTH exome AF: 0.558

GnomAD4 exome Data not reliable, filtered out with message: InbreedingCoeff AF: 0.539 AC: 640377 AN: 1189016 Hom.: 115795 Cov.: 0 AF XY: 0.538 AC XY: 319087 AN XY: 592948

Gnomad4 AFR exome AF: 0.523

Gnomad4 AMR exome AF: 0.604

Gnomad4 ASJ exome AF: 0.515

Gnomad4 EAS exome AF: 0.604

Gnomad4 SAS exome AF: 0.523

Gnomad4 FIN exome AF: 0.527

Gnomad4 NFE exome AF: 0.536

Gnomad4 OTH exome AF: 0.538

GnomAD4 genome Data not reliable, filtered out with message: AS_VQSR AF: 0.612 AC: 56123 AN: 91778 Hom.: 13473 Cov.: 0 AF XY: 0.617 AC XY: 26720 AN XY: 43276

Gnomad4 AFR AF: 0.592

Gnomad4 AMR AF: 0.675

Gnomad4 ASJ AF: 0.589

Gnomad4 EAS AF: 0.677

Gnomad4 SAS AF: 0.609

Gnomad4 FIN AF: 0.650

Gnomad4 NFE AF: 0.600

Gnomad4 OTH AF: 0.647

ClinVar

Significance: Benign

Submissions summary: Benign:1

Revision: criteria provided, single submitter

Submissions by phenotype

not provided Benign:1

Benign, criteria provided, single submitter

clinical testing

GeneDx

Feb 23, 2021

This variant is associated with the following publications: (PMID: 33193662) -

Computational scores

Source: dbNSFP v4.3

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: rs5788645; hg19: chr10-125780752;