12-104517468-T-C

Variant names:

• chr12-104517468-T-C
• rs1795849
• NM_018413.6:c.118+59939T>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.118+59939T>C variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.278 in 152,072 control chromosomes in the GnomAD database, including 6,255 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 0.28 (6255 hom., cov: 31)
• Consequence: CHST11 NM_018413.6 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -2.41
• Publications: 6 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=-0.98).
• BA1: GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.37 is higher than 0.05.

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_018413.6. 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
	CHST11	NM_018413.6	MANE Select	c.118+59939T>C		intron	N/A	NP_060883.1
	CHST11	NM_001173982.2		c.103+59954T>C		intron	N/A	NP_001167453.1

Ensembl Transcripts

Selected	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	CHST11	ENST00000303694.6	TSL:1 MANE Select	c.118+59939T>C		intron	N/A	ENSP00000305725.5
	CHST11	ENST00000549260.5	TSL:1	c.103+59954T>C		intron	N/A	ENSP00000450004.1
	CHST11	ENST00000547956.1	TSL:2	c.118+59939T>C		intron	N/A	ENSP00000449093.1

Frequencies

GnomAD3 genomes AF: 0.278 AC: 42180 AN: 151954 Hom.: 6240 Cov.: 31

Gnomad AFR AF: 0.374

Gnomad AMI AF: 0.326

Gnomad AMR AF: 0.303

Gnomad ASJ AF: 0.215

Gnomad EAS AF: 0.338

Gnomad SAS AF: 0.206

Gnomad FIN AF: 0.133

Gnomad MID AF: 0.220

Gnomad NFE AF: 0.239

Gnomad OTH AF: 0.288

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

GnomAD4 genome AF: 0.278 AC: 42238 AN: 152072 Hom.: 6255 Cov.: 31 AF XY: 0.272 AC XY: 20189 AN XY: 74354

African (AFR) AF: 0.375 AC: 15522 AN: 41422

American (AMR) AF: 0.303 AC: 4626 AN: 15280

Ashkenazi Jewish (ASJ) AF: 0.215 AC: 744 AN: 3468

East Asian (EAS) AF: 0.338 AC: 1750 AN: 5178

South Asian (SAS) AF: 0.204 AC: 986 AN: 4826

European-Finnish (FIN) AF: 0.133 AC: 1411 AN: 10596

Middle Eastern (MID) AF: 0.226 AC: 66 AN: 292

European-Non Finnish (NFE) AF: 0.239 AC: 16235 AN: 67988

Other (OTH) AF: 0.285 AC: 602 AN: 2114

Alfa AF: 0.258 Hom.: 20270

Bravo AF: 0.302

Asia WGS AF: 0.265 AC: 920 AN: 3476

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.98
CADD	Benign	0.45
DANN	Benign	0.60
PhyloP100		-2.4
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: rs1795849; hg19: chr12-104911246;