rs746035

Variant names:

• chr12-104598133-T-C
• rs746035
• NM_018413.6:c.119-3773T>C

Variant summary

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

The NM_018413.6(CHST11):​c.119-3773T>C variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.398 in 152,124 control chromosomes in the GnomAD database, including 12,442 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 0.40 (12442 hom., cov: 32)
• Consequence: CHST11 NM_018413.6 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -2.00
• Publications: 7 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=-0.93).
• BA1: GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.682 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
CHST11	NM_018413.6	c.119-3773T>C		intron_variant	Intron 1 of 2	ENST00000303694.6	NP_060883.1
CHST11	NM_001173982.2	c.104-3773T>C		intron_variant	Intron 1 of 2		NP_001167453.1
CHST11	XM_047428914.1	c.-34+140604T>C		intron_variant	Intron 1 of 1		XP_047284870.1
CHST11	XM_047428915.1	c.-34+140619T>C		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.119-3773T>C		intron_variant	Intron 1 of 2	1	NM_018413.6	ENSP00000305725.5

Frequencies

GnomAD3 genomes AF: 0.398 AC: 60443 AN: 152006 Hom.: 12416 Cov.: 32

Gnomad AFR AF: 0.417

Gnomad AMI AF: 0.302

Gnomad AMR AF: 0.372

Gnomad ASJ AF: 0.446

Gnomad EAS AF: 0.700

Gnomad SAS AF: 0.476

Gnomad FIN AF: 0.328

Gnomad MID AF: 0.392

Gnomad NFE AF: 0.372

Gnomad OTH AF: 0.424

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

GnomAD4 genome AF: 0.398 AC: 60524 AN: 152124 Hom.: 12442 Cov.: 32 AF XY: 0.397 AC XY: 29554 AN XY: 74358

African (AFR) AF: 0.417 AC: 17308 AN: 41478

American (AMR) AF: 0.372 AC: 5693 AN: 15298

Ashkenazi Jewish (ASJ) AF: 0.446 AC: 1547 AN: 3470

East Asian (EAS) AF: 0.701 AC: 3630 AN: 5180

South Asian (SAS) AF: 0.476 AC: 2299 AN: 4828

European-Finnish (FIN) AF: 0.328 AC: 3465 AN: 10578

Middle Eastern (MID) AF: 0.388 AC: 114 AN: 294

European-Non Finnish (NFE) AF: 0.372 AC: 25290 AN: 67978

Other (OTH) AF: 0.428 AC: 904 AN: 2112

Alfa AF: 0.381 Hom.: 4046

Bravo AF: 0.403

Asia WGS AF: 0.600 AC: 2087 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.93
CADD	Benign	0.036
DANN	Benign	0.39
PhyloP100		-2.0
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: rs746035; hg19: chr12-104991911;