12-104457405-C-A

Variant names:

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

Variant summary

Our verdict is Benign. Variant got -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

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]

ACMG classification

Verdict is Benign. Variant got -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 id is 3044683.Status of the report is no_assertion_criteria_provided, 0 stars.
• BS2: High Homozygotes in GnomAdExome4 at 33 AR gene

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
CHST11	NM_018413.6	c.-7C>A		5_prime_UTR_variant	Exon 1 of 3	ENST00000303694.6	NP_060883.1
CHST11	NM_001173982.2	c.-7C>A		5_prime_UTR_variant	Exon 1 of 3		NP_001167453.1
CHST11	XM_047428914.1	c.-158C>A		5_prime_UTR_variant	Exon 1 of 2		XP_047284870.1
CHST11	XM_047428915.1	c.-143C>A		5_prime_UTR_variant	Exon 1 of 2		XP_047284871.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
CHST11	ENST00000303694	c.-7C>A		5_prime_UTR_variant	Exon 1 of 3	1	NM_018413.6	ENSP00000305725.5
CHST11	ENST00000549260	c.-7C>A		5_prime_UTR_variant	Exon 1 of 3	1		ENSP00000450004.1
CHST11	ENST00000547956	c.-7C>A		5_prime_UTR_variant	Exon 1 of 2	2		ENSP00000449093.1
CHST11	ENST00000546689	c.-7C>A		5_prime_UTR_variant	Exon 1 of 2	2		ENSP00000448678.1

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

GnomAD3 exomes AF: 0.00238 AC: 595 AN: 249862 Hom.: 0 AF XY: 0.00246 AC XY: 333 AN XY: 135224

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 SAS 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

Gnomad4 AFR exome AF: 0.00111

Gnomad4 AMR exome AF: 0.00123

Gnomad4 ASJ exome AF: 0.000153

Gnomad4 EAS exome AF: 0.00

Gnomad4 SAS exome AF: 0.0000232

Gnomad4 FIN exome AF: 0.0000375

Gnomad4 NFE exome AF: 0.00627

Gnomad4 OTH exome AF: 0.00520

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

Gnomad4 AFR AF: 0.00118

Gnomad4 AMR AF: 0.000588

Gnomad4 ASJ AF: 0.00

Gnomad4 EAS AF: 0.00

Gnomad4 SAS AF: 0.00

Gnomad4 FIN AF: 0.0000941

Gnomad4 NFE AF: 0.00535

Gnomad4 OTH AF: 0.00190

Alfa AF: 0.00426 Hom.: 1

Bravo AF: 0.00288

EpiCase AF: 0.00496

EpiControl AF: 0.00487

ClinVar

Significance: Likely benign

Submissions summary: Benign:1

Revision: no assertion criteria provided

Submissions by phenotype

CHST11-related disorder Benign:1

Feb 19, 2024

PreventionGenetics, part of Exact Sciences

Significance: Likely benign

Review Status: no assertion criteria provided

Collection Method: clinical testing

This variant is classified as likely benign based on ACMG/AMP sequence variant interpretation guidelines (Richards et al. 2015 PMID: 25741868, with internal and published modifications). -

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.28
CADD	Benign	22
DANN	Benign	0.94

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

Publications

LitVar

Other links and lift over

dbSNP: rs200653714; hg19: chr12-104851183;