NM_018413.6:c.-7C>A

Variant names:

• chr12-104457405-C-A
• rs200653714
• NM_018413.6:c.-7C>A

Variant summary

Our verdict is Benign. The variant received -7 ACMG points: 0P and 7B. BP4_Moderate BP6 BS2

The NM_018413.6(CHST11):​c.-7C>A variant causes a 5 prime UTR change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00484 in 1,609,418 control chromosomes in the GnomAD database, including 34 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Likely benign (no stars).

• Frequency:
  • Genomes: 𝑓 0.0028 (1 hom., cov: 32)
  • Exomes 𝑓: 0.0051 (33 hom.)
• Consequence: CHST11 NM_018413.6 5_prime_UTR
• Clinical Significance: Likely benign no assertion criteria provided B:1
• Conservation: PhyloP100: 3.34
• Publications: 0 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: Ambry Genetics, Labcorp Genetics (formerly Invitae)

ACMG classification

Our verdict: Benign. The variant received -7 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.28).
• BP6: Variant 12-104457405-C-A is Benign according to our data. Variant chr12-104457405-C-A is described in ClinVar as Likely_benign. ClinVar VariationId is 3044683.Status of the report is no_assertion_criteria_provided, 0 stars.
• BS2: High Homozygotes in GnomAdExome4 at 33 AR gene

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

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	CHST11	NM_018413.6	MANE Select	c.-7C>A		5_prime_UTR	Exon 1 of 3	NP_060883.1	Q9NPF2-1
	CHST11	NM_001173982.2		c.-7C>A		5_prime_UTR	Exon 1 of 3	NP_001167453.1	Q9NPF2-2

Ensembl Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	CHST11	ENST00000303694.6	TSL:1 MANE Select	c.-7C>A		5_prime_UTR	Exon 1 of 3	ENSP00000305725.5	Q9NPF2-1
	CHST11	ENST00000549260.5	TSL:1	c.-7C>A		5_prime_UTR	Exon 1 of 3	ENSP00000450004.1	Q9NPF2-2
	CHST11	ENST00000547956.1	TSL:2	c.-7C>A		5_prime_UTR	Exon 1 of 2	ENSP00000449093.1	F8VXK7

Frequencies

GnomAD3 genomes AF: 0.00282 AC: 429 AN: 152210 Hom.: 1 Cov.: 32

Gnomad AFR AF: 0.00118

Gnomad AMI AF: 0.00219

Gnomad AMR AF: 0.000589

Gnomad ASJ AF: 0.00

Gnomad EAS AF: 0.00

Gnomad SAS AF: 0.00

Gnomad FIN AF: 0.0000941

Gnomad MID AF: 0.00

Gnomad NFE AF: 0.00535

Gnomad OTH AF: 0.00191

GnomAD2 exomes AF: 0.00238 AC: 595 AN: 249862 AF XY: 0.00246

Gnomad AFR exome AF: 0.000929

Gnomad AMR exome AF: 0.00119

Gnomad ASJ exome AF: 0.00

Gnomad EAS exome AF: 0.00

Gnomad FIN exome AF: 0.0000464

Gnomad NFE exome AF: 0.00461

Gnomad OTH exome AF: 0.00310

GnomAD4 exome AF: 0.00505 AC: 7365 AN: 1457092 Hom.: 33 Cov.: 29 AF XY: 0.00483 AC XY: 3504 AN XY: 725214

African (AFR) AF: 0.00111 AC: 37 AN: 33374

American (AMR) AF: 0.00123 AC: 55 AN: 44624

Ashkenazi Jewish (ASJ) AF: 0.000153 AC: 4 AN: 26096

East Asian (EAS) AF: 0.00 AC: 0 AN: 39664

South Asian (SAS) AF: 0.0000232 AC: 2 AN: 86122

European-Finnish (FIN) AF: 0.0000375 AC: 2 AN: 53342

Middle Eastern (MID) AF: 0.00 AC: 0 AN: 5716

European-Non Finnish (NFE) AF: 0.00627 AC: 6952 AN: 1107982

Other (OTH) AF: 0.00520 AC: 313 AN: 60172

GnomAD4 genome AF: 0.00282 AC: 429 AN: 152326 Hom.: 1 Cov.: 32 AF XY: 0.00246 AC XY: 183 AN XY: 74508

African (AFR) AF: 0.00118 AC: 49 AN: 41586

American (AMR) AF: 0.000588 AC: 9 AN: 15312

Ashkenazi Jewish (ASJ) AF: 0.00 AC: 0 AN: 3470

East Asian (EAS) AF: 0.00 AC: 0 AN: 5174

South Asian (SAS) AF: 0.00 AC: 0 AN: 4828

European-Finnish (FIN) AF: 0.0000941 AC: 1 AN: 10630

Middle Eastern (MID) AF: 0.00 AC: 0 AN: 294

European-Non Finnish (NFE) AF: 0.00535 AC: 364 AN: 68010

Other (OTH) AF: 0.00190 AC: 4 AN: 2110

Alfa AF: 0.00426 Hom.: 1

Bravo AF: 0.00288

EpiCase AF: 0.00496

EpiControl AF: 0.00487

ClinVar

ClinVar submissions

Significance: Likely benign

Revision: no assertion criteria provided

Pathogenic	VUS	Benign	Condition
-	-	1	CHST11-related disorder (1)

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.28
CADD	Benign	22
DANN	Benign	0.94
PhyloP100		3.3
PromoterAI		-0.078	Neutral
Mutation Taster		=290/10	polymorphism

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: rs200653714; hg19: chr12-104851183;