rs7894516

chr10-71969892-A-Cchr10-71969892-A-T

Variant summary

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

The NM_004273.5(CHST3):c.-108+5198A>C variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.308 in 152,138 control chromosomes in the GnomAD database, including 8,524 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 0.31 (8524 hom., cov: 33)
• Consequence: CHST3 NM_004273.5 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 0.0120

Genes affected

CHST3 (HGNC:1971): (carbohydrate sulfotransferase 3) This gene encodes an enzyme which catalyzes the sulfation of chondroitin, a proteoglycan found in the extracellular matrix and most cells which is involved in cell migration and differentiation. Mutations in this gene are associated with spondylepiphyseal dysplasia and humerospinal dysostosis. [provided by RefSeq, Mar 2009]

ACMG classification

Verdict is Benign. Variant got -12 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.78).
• BA1: GnomAd4 highest subpopulation (SAS) allele frequency at 95% confidence interval = 0.452 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
CHST3	NM_004273.5	c.-108+5198A>C		intron_variant		ENST00000373115.5
CHST3	XM_006718075.5	c.-108+4417A>C		intron_variant
CHST3	XM_047426022.1	c.-108+4992A>C		intron_variant

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
CHST3	ENST00000373115.5	c.-108+5198A>C		intron_variant		1	NM_004273.5	P1

Frequencies

GnomAD3 genomes AF: 0.308 AC: 46774 AN: 152020 Hom.: 8521 Cov.: 33

Gnomad AFR AF: 0.110

Gnomad AMI AF: 0.230

Gnomad AMR AF: 0.297

Gnomad ASJ AF: 0.413

Gnomad EAS AF: 0.187

Gnomad SAS AF: 0.466

Gnomad FIN AF: 0.430

Gnomad MID AF: 0.459

Gnomad NFE AF: 0.404

Gnomad OTH AF: 0.318

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

GnomAD4 genome AF: 0.308 AC: 46783 AN: 152138 Hom.: 8524 Cov.: 33 AF XY: 0.313 AC XY: 23289 AN XY: 74364

Gnomad4 AFR AF: 0.110

Gnomad4 AMR AF: 0.297

Gnomad4 ASJ AF: 0.413

Gnomad4 EAS AF: 0.186

Gnomad4 SAS AF: 0.468

Gnomad4 FIN AF: 0.430

Gnomad4 NFE AF: 0.404

Gnomad4 OTH AF: 0.320

Alfa AF: 0.390 Hom.: 15124

Bravo AF: 0.284

Asia WGS AF: 0.312 AC: 1088 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.78
Cadd	Benign	6.2
Dann	Benign	0.75

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: rs7894516; hg19: chr10-73729650;