rs2394848

Positions:

• chr10-71990315-G-A

Variant summary

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

The NM_004273.5(CHST3):​c.-107-15421G>A variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.349 in 152,004 control chromosomes in the GnomAD database, including 10,966 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 0.35 (10966 hom., cov: 31)
• Consequence: CHST3 NM_004273.5 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -1.59

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=-1.02).
• BA1: GnomAd4 highest subpopulation (NFE) allele frequency at 95% confidence interval = 0.47 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
CHST3	NM_004273.5	c.-107-15421G>A		intron_variant		ENST00000373115.5	NP_004264.2
CHST3	XM_006718075.5	c.-107-15421G>A		intron_variant			XP_006718138.1
CHST3	XM_011540369.3	c.-107-15421G>A		intron_variant			XP_011538671.1
CHST3	XM_047426022.1	c.-107-15421G>A		intron_variant			XP_047281978.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
CHST3	ENST00000373115.5	c.-107-15421G>A		intron_variant		1	NM_004273.5	ENSP00000362207.4

Frequencies

GnomAD3 genomes AF: 0.350 AC: 53132 AN: 151886 Hom.: 10966 Cov.: 31

Gnomad AFR AF: 0.133

Gnomad AMI AF: 0.430

Gnomad AMR AF: 0.386

Gnomad ASJ AF: 0.416

Gnomad EAS AF: 0.113

Gnomad SAS AF: 0.316

Gnomad FIN AF: 0.442

Gnomad MID AF: 0.401

Gnomad NFE AF: 0.474

Gnomad OTH AF: 0.385

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

GnomAD4 genome AF: 0.349 AC: 53119 AN: 152004 Hom.: 10966 Cov.: 31 AF XY: 0.346 AC XY: 25719 AN XY: 74266

Gnomad4 AFR AF: 0.133

Gnomad4 AMR AF: 0.386

Gnomad4 ASJ AF: 0.416

Gnomad4 EAS AF: 0.113

Gnomad4 SAS AF: 0.316

Gnomad4 FIN AF: 0.442

Gnomad4 NFE AF: 0.474

Gnomad4 OTH AF: 0.379

Alfa AF: 0.403 Hom.: 1675

Bravo AF: 0.336

Asia WGS AF: 0.195 AC: 682 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	1.0
DANN	Benign	0.33

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: rs2394848; hg19: chr10-73750073;