rs835488

Variant names:

• chr12-104667230-C-T
• rs835488
• NM_018413.6:c.204+65239C>T

Variant summary

Our verdict is Benign. The variant received -12 ACMG points: 0P and 12B. BP4_Strong BA1

The NM_018413.6(CHST11):​c.204+65239C>T variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.41 in 151,908 control chromosomes in the GnomAD database, including 13,571 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 0.41 (13571 hom., cov: 31)
• Consequence: CHST11 NM_018413.6 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.597
• Publications: 2 publications found

Genes affected

CHST11 (HGNC:17422): (carbohydrate sulfotransferase 11) The protein encoded by this gene belongs to the sulfotransferase 2 family. It is localized to the golgi membrane, and catalyzes the transfer of sulfate to position 4 of the N-acetylgalactosamine (GalNAc) residue of chondroitin. Chondroitin sulfate constitutes the predominant proteoglycan present in cartilage, and is distributed on the surfaces of many cells and extracellular matrices. A chromosomal translocation involving this gene and IgH, t(12;14)(q23;q32), has been reported in a patient with B-cell chronic lymphocytic leukemia. Alternatively spliced transcript variants encoding different isoforms have been found for this gene. [provided by RefSeq, Aug 2011]

CHST11 Gene-Disease associations (from GenCC):

• osteochondrodysplasia, brachydactyly, and overlapping malformed digits

  Inheritance: AR Classification: STRONG, LIMITED Submitted by: Labcorp Genetics (formerly Invitae), Ambry Genetics

ACMG classification

Our verdict: Benign. The variant received -12 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.9).
• BA1: GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.558 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
CHST11	NM_018413.6	c.204+65239C>T		intron_variant	Intron 2 of 2	ENST00000303694.6	NP_060883.1
CHST11	NM_001173982.2	c.189+65239C>T		intron_variant	Intron 2 of 2		NP_001167453.1
CHST11	XM_047428914.1	c.-33-89719C>T		intron_variant	Intron 1 of 1		XP_047284870.1
CHST11	XM_047428915.1	c.-33-89719C>T		intron_variant	Intron 1 of 1		XP_047284871.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
CHST11	ENST00000303694.6	c.204+65239C>T		intron_variant	Intron 2 of 2	1	NM_018413.6	ENSP00000305725.5
CHST11	ENST00000549260.5	c.189+65239C>T		intron_variant	Intron 2 of 2	1		ENSP00000450004.1
CHST11	ENST00000549016.1	c.84+65239C>T		intron_variant	Intron 2 of 2	4		ENSP00000449095.1

Frequencies

GnomAD3 genomes AF: 0.409 AC: 62142 AN: 151790 Hom.: 13529 Cov.: 31

Gnomad AFR AF: 0.564

Gnomad AMI AF: 0.480

Gnomad AMR AF: 0.337

Gnomad ASJ AF: 0.372

Gnomad EAS AF: 0.365

Gnomad SAS AF: 0.420

Gnomad FIN AF: 0.299

Gnomad MID AF: 0.366

Gnomad NFE AF: 0.353

Gnomad OTH AF: 0.407

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

GnomAD4 genome AF: 0.410 AC: 62242 AN: 151908 Hom.: 13571 Cov.: 31 AF XY: 0.406 AC XY: 30113 AN XY: 74234

African (AFR) AF: 0.564 AC: 23368 AN: 41420

American (AMR) AF: 0.337 AC: 5144 AN: 15258

Ashkenazi Jewish (ASJ) AF: 0.372 AC: 1291 AN: 3472

East Asian (EAS) AF: 0.365 AC: 1881 AN: 5156

South Asian (SAS) AF: 0.420 AC: 2018 AN: 4804

European-Finnish (FIN) AF: 0.299 AC: 3155 AN: 10550

Middle Eastern (MID) AF: 0.360 AC: 105 AN: 292

European-Non Finnish (NFE) AF: 0.353 AC: 23973 AN: 67942

Other (OTH) AF: 0.414 AC: 871 AN: 2106

Alfa AF: 0.391 Hom.: 2392

Bravo AF: 0.418

Asia WGS AF: 0.451 AC: 1565 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.90
CADD	Benign	0.81
DANN	Benign	0.52
PhyloP100		-0.60
Mutation Taster		=100/0	polymorphism (auto)

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: rs835488; hg19: chr12-105061008;