12-104630627-C-T

Variant names:

• chr12-104630627-C-T
• rs10507180
• NM_018413.6:c.204+28636C>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+28636C>T variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.307 in 152,012 control chromosomes in the GnomAD database, including 8,025 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 (8025 hom., cov: 32)
• Consequence: CHST11 NM_018413.6 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -1.70
• 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=-0.94).
• BA1: GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.518 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
CHST11	NM_018413.6	c.204+28636C>T		intron_variant	Intron 2 of 2	ENST00000303694.6	NP_060883.1
CHST11	NM_001173982.2	c.189+28636C>T		intron_variant	Intron 2 of 2		NP_001167453.1
CHST11	XM_047428914.1	c.-33-126322C>T		intron_variant	Intron 1 of 1		XP_047284870.1
CHST11	XM_047428915.1	c.-33-126322C>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+28636C>T		intron_variant	Intron 2 of 2	1	NM_018413.6	ENSP00000305725.5
CHST11	ENST00000549260.5	c.189+28636C>T		intron_variant	Intron 2 of 2	1		ENSP00000450004.1
CHST11	ENST00000549016.1	c.84+28636C>T		intron_variant	Intron 2 of 2	4		ENSP00000449095.1

Frequencies

GnomAD3 genomes AF: 0.307 AC: 46647 AN: 151894 Hom.: 8027 Cov.: 32

Gnomad AFR AF: 0.145

Gnomad AMI AF: 0.359

Gnomad AMR AF: 0.311

Gnomad ASJ AF: 0.400

Gnomad EAS AF: 0.535

Gnomad SAS AF: 0.339

Gnomad FIN AF: 0.368

Gnomad MID AF: 0.329

Gnomad NFE AF: 0.369

Gnomad OTH AF: 0.333

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

GnomAD4 genome AF: 0.307 AC: 46645 AN: 152012 Hom.: 8025 Cov.: 32 AF XY: 0.308 AC XY: 22887 AN XY: 74284

African (AFR) AF: 0.145 AC: 6011 AN: 41474

American (AMR) AF: 0.312 AC: 4759 AN: 15276

Ashkenazi Jewish (ASJ) AF: 0.400 AC: 1389 AN: 3470

East Asian (EAS) AF: 0.534 AC: 2754 AN: 5154

South Asian (SAS) AF: 0.340 AC: 1636 AN: 4816

European-Finnish (FIN) AF: 0.368 AC: 3883 AN: 10550

Middle Eastern (MID) AF: 0.327 AC: 96 AN: 294

European-Non Finnish (NFE) AF: 0.369 AC: 25098 AN: 67958

Other (OTH) AF: 0.328 AC: 692 AN: 2110

Alfa AF: 0.345 Hom.: 14897

Bravo AF: 0.300

Asia WGS AF: 0.389 AC: 1353 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.94
CADD	Benign	0.33
DANN	Benign	0.65
PhyloP100		-1.7
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: rs10507180; hg19: chr12-105024405;