16-75473200-G-A

Variant summary

Our verdict is Benign. Variant got -14 ACMG points: 0P and 14B. BP4_Strong BP6_Moderate BS1 BS2

The NM_021615.5(CHST6):c.*5441C>T variant causes a 3 prime UTR change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0125 in 152,276 control chromosomes in the GnomAD database, including 45 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★).

• Frequency:
  • Genomes: 𝑓 0.012 (45 hom., cov: 33)
  • Exomes 𝑓: 0.0 (0 hom.)
  • Failed GnomAD Quality Control
• Consequence: CHST6 NM_021615.5 3_prime_UTR
• Clinical Significance: Benign criteria provided, single submitter B:1
• Conservation: PhyloP100: -0.304

Genes affected

CHST6 (HGNC:6938): (carbohydrate sulfotransferase 6) The protein encoded by this gene is an enzyme that catalyzes the transfer of a sulfate group to the GlcNAc residues of keratan. Keratan sulfate helps maintain corneal transparency. Defects in this gene are a cause of macular corneal dystrophy (MCD). [provided by RefSeq, Jan 2010]

ACMG classification

Verdict is Benign. Variant got -14 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.96).
• BP6: Variant 16-75473200-G-A is Benign according to our data. Variant chr16-75473200-G-A is described in ClinVar as [Benign]. Clinvar id is 320506.Status of the report is criteria_provided_single_submitter, 1 stars.
• BS1: Variant frequency is greater than expected in population afr. gnomad4 allele frequency = 0.0125 (1898/152276) while in subpopulation AFR AF= 0.0376 (1563/41558). AF 95% confidence interval is 0.0361. There are 45 homozygotes in gnomad4. There are 897 alleles in male gnomad4 subpopulation. Median coverage is 33. This position pass quality control queck.
• BS2: High Homozygotes in GnomAd at 46 AR gene

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
CHST6	NM_021615.5	c.*5441C>T		3_prime_UTR_variant	3/3	ENST00000332272.9
CHST6	NR_163480.1	n.1001C>T		non_coding_transcript_exon_variant	4/4
CHST6	NR_163481.1	n.845C>T		non_coding_transcript_exon_variant	3/3

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
CHST6	ENST00000332272.9	c.*5441C>T		3_prime_UTR_variant	3/3	3	NM_021615.5	P1
CHST6	ENST00000649824.1	c.*866C>T		3_prime_UTR_variant, NMD_transcript_variant	4/4

Frequencies

GnomAD3 genomes AF: 0.0125 AC: 1895 AN: 152158 Hom.: 46 Cov.: 33

Gnomad AFR AF: 0.0376

Gnomad AMI AF: 0.00

Gnomad AMR AF: 0.00517

Gnomad ASJ AF: 0.0536

Gnomad EAS AF: 0.000578

Gnomad SAS AF: 0.00104

Gnomad FIN AF: 0.000283

Gnomad MID AF: 0.00316

Gnomad NFE AF: 0.000514

Gnomad OTH AF: 0.0110

GnomAD4 exome Data not reliable, filtered out with message: AC0 AF: 0.00 AC: 0 AN: 112 Hom.: 0 Cov.: 0 AF XY: 0.00 AC XY: 0 AN XY: 72

Gnomad4 AFR exome AF: 0.00

Gnomad4 AMR exome AF: 0.00

Gnomad4 FIN exome AF: 0.00

Gnomad4 NFE exome AF: 0.00

Gnomad4 OTH exome AF: 0.00

GnomAD4 genome AF: 0.0125 AC: 1898 AN: 152276 Hom.: 45 Cov.: 33 AF XY: 0.0120 AC XY: 897 AN XY: 74442

Gnomad4 AFR AF: 0.0376

Gnomad4 AMR AF: 0.00517

Gnomad4 ASJ AF: 0.0536

Gnomad4 EAS AF: 0.000579

Gnomad4 SAS AF: 0.00104

Gnomad4 FIN AF: 0.000283

Gnomad4 NFE AF: 0.000514

Gnomad4 OTH AF: 0.0109

Alfa AF: 0.00481 Hom.: 12

Bravo AF: 0.0148

Asia WGS AF: 0.00318 AC: 11 AN: 3478

ClinVar

Significance: Benign

Submissions summary: Benign:1

Revision: criteria provided, single submitter

Submissions by phenotype

Macular corneal dystrophy Benign:1

Benign, criteria provided, single submitter

clinical testing

Illumina Laboratory Services, Illumina

Jan 12, 2018

This variant was observed in the ICSL laboratory as part of a predisposition screen in an ostensibly healthy population. It had not been previously curated by ICSL or reported in the Human Gene Mutation Database (HGMD: prior to June 1st, 2018), and was therefore a candidate for classification through an automated scoring system. Utilizing variant allele frequency, disease prevalence and penetrance estimates, and inheritance mode, an automated score was calculated to assess if this variant is too frequent to cause the disease. Based on the score and internal cut-off values, a variant classified as benign is not then subjected to further curation. The score for this variant resulted in a classification of benign for this disease. -

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.96
Cadd	Benign	1.7
Dann	Benign	0.50

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: rs74742116; hg19: chr16-75507098;