NM_018413.6:c.205-55515A>G

Variant names:

• chr12-104701434-A-G
• rs167490
• NM_018413.6:c.205-55515A>G

Variant summary

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

The NM_018413.6(CHST11):​c.205-55515A>G variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.831 in 152,130 control chromosomes in the GnomAD database, including 52,640 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 0.83 (52640 hom., cov: 31)
• Consequence: CHST11 NM_018413.6 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -1.42
• 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=-0.99).
• BA1: GnomAd4 highest subpopulation (SAS) allele frequency at 95% confidence interval = 0.873 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.205-55515A>G		intron	N/A	NP_060883.1
	CHST11	NM_001173982.2		c.190-55515A>G		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.205-55515A>G		intron	N/A	ENSP00000305725.5
	CHST11	ENST00000549260.5	TSL:1	c.190-55515A>G		intron	N/A	ENSP00000450004.1
	CHST11	ENST00000549016.1	TSL:4	c.85-55515A>G		intron	N/A	ENSP00000449095.1

Frequencies

GnomAD3 genomes AF: 0.831 AC: 126363 AN: 152012 Hom.: 52578 Cov.: 31

Gnomad AFR AF: 0.863

Gnomad AMI AF: 0.793

Gnomad AMR AF: 0.843

Gnomad ASJ AF: 0.804

Gnomad EAS AF: 0.802

Gnomad SAS AF: 0.896

Gnomad FIN AF: 0.800

Gnomad MID AF: 0.747

Gnomad NFE AF: 0.814

Gnomad OTH AF: 0.823

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

GnomAD4 genome AF: 0.831 AC: 126485 AN: 152130 Hom.: 52640 Cov.: 31 AF XY: 0.833 AC XY: 61943 AN XY: 74378

African (AFR) AF: 0.863 AC: 35825 AN: 41508

American (AMR) AF: 0.843 AC: 12890 AN: 15288

Ashkenazi Jewish (ASJ) AF: 0.804 AC: 2790 AN: 3470

East Asian (EAS) AF: 0.802 AC: 4145 AN: 5166

South Asian (SAS) AF: 0.896 AC: 4323 AN: 4826

European-Finnish (FIN) AF: 0.800 AC: 8453 AN: 10570

Middle Eastern (MID) AF: 0.748 AC: 220 AN: 294

European-Non Finnish (NFE) AF: 0.814 AC: 55372 AN: 67986

Other (OTH) AF: 0.826 AC: 1747 AN: 2114

Alfa AF: 0.820 Hom.: 84724

Bravo AF: 0.836

Asia WGS AF: 0.851 AC: 2962 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.99
CADD	Benign	0.10
DANN	Benign	0.24
PhyloP100		-1.4
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: rs167490; hg19: chr12-105095212;