rs582736

Variant names:

• chr15-40472350-G-A
• rs582736
• NM_130468.4:c.*6G>A

Variant summary

Our verdict is Benign. The variant received -20 ACMG points: 0P and 20B. BP4_Strong BP6_Very_Strong BA1

The NM_130468.4(CHST14):​c.*6G>A variant causes a 3 prime UTR change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0884 in 1,589,784 control chromosomes in the GnomAD database, including 7,958 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★★).

• Frequency:
  • Genomes: 𝑓 0.14 (1927 hom., cov: 32)
  • Exomes 𝑓: 0.083 (6031 hom.)
• Consequence: CHST14 NM_130468.4 3_prime_UTR
• Clinical Significance: Benign criteria provided, multiple submitters, no conflicts B:4
• Conservation: PhyloP100: 2.31
• Publications: 15 publications found

Genes affected

CHST14 (HGNC:24464): (carbohydrate sulfotransferase 14) This gene encodes a member of the HNK-1 family of sulfotransferases. The encoded protein transfers sulfate to the C-4 hydroxyl of N-acetylgalactosamine residues in dermatan sulfate. Mutations in this gene have been associated with adducted thumb-clubfoot syndrome.[provided by RefSeq, Mar 2010]

CHST14 Gene-Disease associations (from GenCC):

• Ehlers-Danlos syndrome, musculocontractural type 1

  Inheritance: AR Classification: DEFINITIVE, STRONG Submitted by: Genomics England PanelApp, G2P, PanelApp Australia, Ambry Genetics, Labcorp Genetics (formerly Invitae)
• Ehlers-Danlos syndrome, musculocontractural type

  Inheritance: AR Classification: SUPPORTIVE Submitted by: Orphanet

ACMG classification

Our verdict: Benign. The variant received -20 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.83).
• BP6: Variant 15-40472350-G-A is Benign according to our data. Variant chr15-40472350-G-A is described in ClinVar as Benign. ClinVar VariationId is 128769.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars.
• BA1: GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.268 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
CHST14	NM_130468.4	c.*6G>A		3_prime_UTR_variant	Exon 1 of 1	ENST00000306243.7	NP_569735.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
CHST14	ENST00000306243.7	c.*6G>A		3_prime_UTR_variant	Exon 1 of 1	6	NM_130468.4	ENSP00000307297.6
CHST14	ENST00000559991.1	c.*6G>A		3_prime_UTR_variant	Exon 2 of 2	5		ENSP00000453882.1

Frequencies

GnomAD3 genomes AF: 0.135 AC: 20531 AN: 152142 Hom.: 1916 Cov.: 32

Gnomad AFR AF: 0.272

Gnomad AMI AF: 0.0833

Gnomad AMR AF: 0.0795

Gnomad ASJ AF: 0.0403

Gnomad EAS AF: 0.0961

Gnomad SAS AF: 0.129

Gnomad FIN AF: 0.0831

Gnomad MID AF: 0.111

Gnomad NFE AF: 0.0821

Gnomad OTH AF: 0.103

GnomAD2 exomes AF: 0.0980 AC: 22732 AN: 231868 AF XY: 0.0969

Gnomad AFR exome AF: 0.278

Gnomad AMR exome AF: 0.0790

Gnomad ASJ exome AF: 0.0386

Gnomad EAS exome AF: 0.0953

Gnomad FIN exome AF: 0.0807

Gnomad NFE exome AF: 0.0778

Gnomad OTH exome AF: 0.0798

GnomAD4 exome AF: 0.0834 AC: 119885 AN: 1437524 Hom.: 6031 Cov.: 33 AF XY: 0.0848 AC XY: 60366 AN XY: 712278

African (AFR) AF: 0.276 AC: 9080 AN: 32842

American (AMR) AF: 0.0791 AC: 3337 AN: 42206

Ashkenazi Jewish (ASJ) AF: 0.0404 AC: 987 AN: 24404

East Asian (EAS) AF: 0.0789 AC: 3109 AN: 39428

South Asian (SAS) AF: 0.130 AC: 10690 AN: 82374

European-Finnish (FIN) AF: 0.0801 AC: 4214 AN: 52620

Middle Eastern (MID) AF: 0.105 AC: 594 AN: 5642

European-Non Finnish (NFE) AF: 0.0750 AC: 82464 AN: 1098796

Other (OTH) AF: 0.0914 AC: 5410 AN: 59212

GnomAD4 genome AF: 0.135 AC: 20578 AN: 152260 Hom.: 1927 Cov.: 32 AF XY: 0.133 AC XY: 9900 AN XY: 74446

African (AFR) AF: 0.272 AC: 11308 AN: 41512

American (AMR) AF: 0.0796 AC: 1219 AN: 15310

Ashkenazi Jewish (ASJ) AF: 0.0403 AC: 140 AN: 3472

East Asian (EAS) AF: 0.0957 AC: 496 AN: 5182

South Asian (SAS) AF: 0.129 AC: 625 AN: 4828

European-Finnish (FIN) AF: 0.0831 AC: 881 AN: 10604

Middle Eastern (MID) AF: 0.0986 AC: 29 AN: 294

European-Non Finnish (NFE) AF: 0.0821 AC: 5586 AN: 68034

Other (OTH) AF: 0.103 AC: 218 AN: 2112

Alfa AF: 0.0984 Hom.: 1490

Bravo AF: 0.141

Asia WGS AF: 0.111 AC: 384 AN: 3478

ClinVar

Significance: Benign

Submissions summary: Benign:4

Revision: criteria provided, multiple submitters, no conflicts

Submissions by phenotype

not specified Benign:3

Aug 15, 2013

Genetic Services Laboratory, University of Chicago

Significance: Benign

Review Status: criteria provided, single submitter

Collection Method: clinical testing

- -

Oct 06, 2016

GeneDx

Significance: Benign

Review Status: criteria provided, single submitter

Collection Method: clinical testing

This variant is considered likely benign or benign based on one or more of the following criteria: it is a conservative change, it occurs at a poorly conserved position in the protein, it is predicted to be benign by multiple in silico algorithms, and/or has population frequency not consistent with disease. -

-

PreventionGenetics, part of Exact Sciences

Significance: Benign

Review Status: criteria provided, single submitter

Collection Method: clinical testing

- -

not provided Benign:1

-

Breakthrough Genomics, Breakthrough Genomics

Significance: Benign

Review Status: criteria provided, single submitter

Collection Method: not provided

- -

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.83
CADD	Benign	9.9
DANN	Benign	0.77
PhyloP100		2.3
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: rs582736; hg19: chr15-40764549; COSMIC: COSV60379629; COSMIC: COSV60379629;