10-124008578-C-G

Variant names:

• chr10-124008578-C-G
• rs12915
• NM_001270764.2:c.*1571G>C

Variant summary

Our verdict is Likely benign. The variant received -2 ACMG points: 2P and 4B. PM2 BP4_Strong

The NM_015892.5(CHST15):​c.*1571G>C variant causes a 3 prime UTR change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00000232 in 860,540 control chromosomes in the GnomAD database, with no homozygous occurrence. 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: not found (cov: 32)
  • Exomes 𝑓: 0.0000023 (0 hom.)
• Consequence: CHST15 NM_015892.5 3_prime_UTR
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.299
• Publications: 7 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]

ACMG classification

Our verdict: Likely_benign. The variant received -2 ACMG points.

• PM2: Very rare variant in population databases, with high coverage
• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.85).

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_015892.5. You can select a different transcript below to see updated ACMG assignments.

RefSeq Transcripts

Selected	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	CHST15	NM_001270764.2	MANE Select	c.*1571G>C		3_prime_UTR	Exon 8 of 8	NP_001257693.1
	CHST15	NM_015892.5		c.*1571G>C		3_prime_UTR	Exon 8 of 8	NP_056976.2

Ensembl Transcripts

Selected	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	CHST15	ENST00000435907.6	TSL:1 MANE Select	c.*1571G>C		3_prime_UTR	Exon 8 of 8	ENSP00000402394.1
	CHST15	ENST00000346248.7	TSL:1	c.*1571G>C		3_prime_UTR	Exon 8 of 8	ENSP00000333947.6
	CHST15	ENST00000874549.1		c.*1571G>C		3_prime_UTR	Exon 8 of 8	ENSP00000544608.1

Frequencies

GnomAD3 genomes Cov.: 32

GnomAD4 exome AF: 0.00000232 AC: 2 AN: 860540 Hom.: 0 Cov.: 35 AF XY: 0.00000250 AC XY: 1 AN XY: 399732

African (AFR) AF: 0.00 AC: 0 AN: 16800

American (AMR) AF: 0.00 AC: 0 AN: 3366

Ashkenazi Jewish (ASJ) AF: 0.00 AC: 0 AN: 5718

East Asian (EAS) AF: 0.00 AC: 0 AN: 5334

South Asian (SAS) AF: 0.00 AC: 0 AN: 20734

European-Finnish (FIN) AF: 0.00 AC: 0 AN: 1258

Middle Eastern (MID) AF: 0.00 AC: 0 AN: 1694

European-Non Finnish (NFE) AF: 0.00000257 AC: 2 AN: 777126

Other (OTH) AF: 0.00 AC: 0 AN: 28510

GnomAD4 genome Cov.: 32

Alfa AF: 0.00 Hom.: 6509

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.85
CADD	Benign	1.8
DANN	Benign	0.53
PhyloP100		-0.30

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: rs12915; hg19: chr10-125768094;