rs61740901

chr16-75479571-T-G

Variant summary

Our verdict is Benign. Variant got -21 ACMG points: 0P and 21B. BP4_Strong BP6_Very_Strong BP7 BS1 BS2

The NM_021615.5(CHST6):c.258A>C(p.Ala86=) variant causes a synonymous change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0031 in 1,612,988 control chromosomes in the GnomAD database, including 104 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★★).

• Frequency:
  • Genomes: 𝑓 0.013 (43 hom., cov: 33)
  • Exomes 𝑓: 0.0021 (61 hom.)
• Consequence: CHST6 NM_021615.5 synonymous
• Clinical Significance: Benign criteria provided, multiple submitters, no conflicts B:2
• Conservation: PhyloP100: -3.99

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]

(HGNC:):

ACMG classification

Verdict is Benign. Variant got -21 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.95).
• BP6: Variant 16-75479571-T-G is Benign according to our data. Variant chr16-75479571-T-G is described in ClinVar as [Benign]. Clinvar id is 320613.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars.
• BP7: Synonymous conserved (PhyloP=-3.99 with no splicing effect.
• BS1: Variant frequency is greater than expected in population afr. gnomad4 allele frequency = 0.0126 (1916/152318) while in subpopulation AFR AF= 0.0398 (1655/41570). AF 95% confidence interval is 0.0382. There are 43 homozygotes in gnomad4. There are 904 alleles in male gnomad4 subpopulation. Median coverage is 33. This position pass quality control queck.
• BS2: High Homozygotes in GnomAd at 44 AR gene

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
CHST6	NM_021615.5	c.258A>C	p.Ala86=	synonymous_variant	3/3	ENST00000332272.9
CHST6	NR_163480.1	n.733+2246A>C		intron_variant, non_coding_transcript_variant
CHST6	NR_163481.1	n.577+2246A>C		intron_variant, non_coding_transcript_variant

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
CHST6	ENST00000332272.9	c.258A>C	p.Ala86=	synonymous_variant	3/3	3	NM_021615.5	P1
	ENST00000530512.3	n.425+3251T>G		intron_variant, non_coding_transcript_variant		4

Frequencies

GnomAD3 genomes AF: 0.0126 AC: 1913 AN: 152200 Hom.: 44 Cov.: 33

Gnomad AFR AF: 0.0399

Gnomad AMI AF: 0.00

Gnomad AMR AF: 0.00589

Gnomad ASJ AF: 0.0340

Gnomad EAS AF: 0.00

Gnomad SAS AF: 0.000413

Gnomad FIN AF: 0.00

Gnomad MID AF: 0.00316

Gnomad NFE AF: 0.000397

Gnomad OTH AF: 0.0110

GnomAD3 exomes AF: 0.00501 AC: 1250 AN: 249294 Hom.: 19 AF XY: 0.00412 AC XY: 558 AN XY: 135424

Gnomad AFR exome AF: 0.0436

Gnomad AMR exome AF: 0.00368

Gnomad ASJ exome AF: 0.0330

Gnomad EAS exome AF: 0.00

Gnomad SAS exome AF: 0.0000327

Gnomad FIN exome AF: 0.00

Gnomad NFE exome AF: 0.000553

Gnomad OTH exome AF: 0.00525

GnomAD4 exome AF: 0.00211 AC: 3080 AN: 1460670 Hom.: 61 Cov.: 32 AF XY: 0.00197 AC XY: 1429 AN XY: 726676

Gnomad4 AFR exome AF: 0.0414

Gnomad4 AMR exome AF: 0.00389

Gnomad4 ASJ exome AF: 0.0324

Gnomad4 EAS exome AF: 0.00

Gnomad4 SAS exome AF: 0.000151

Gnomad4 FIN exome AF: 0.00

Gnomad4 NFE exome AF: 0.000288

Gnomad4 OTH exome AF: 0.00543

GnomAD4 genome AF: 0.0126 AC: 1916 AN: 152318 Hom.: 43 Cov.: 33 AF XY: 0.0121 AC XY: 904 AN XY: 74490

Gnomad4 AFR AF: 0.0398

Gnomad4 AMR AF: 0.00588

Gnomad4 ASJ AF: 0.0340

Gnomad4 EAS AF: 0.00

Gnomad4 SAS AF: 0.000414

Gnomad4 FIN AF: 0.00

Gnomad4 NFE AF: 0.000397

Gnomad4 OTH AF: 0.0109

Alfa AF: 0.00873 Hom.: 8

Bravo AF: 0.0150

Asia WGS AF: 0.00318 AC: 11 AN: 3478

EpiCase AF: 0.000818

EpiControl AF: 0.000830

ClinVar

Significance: Benign

Submissions summary: Benign:2

Revision: criteria provided, multiple submitters, no conflicts

Submissions by phenotype

Macular corneal dystrophy Benign:2

Benign, criteria provided, single submitter	clinical testing	Illumina Laboratory Services, Illumina	Jan 13, 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. -
Benign, criteria provided, single submitter	clinical testing	Invitae	Jan 22, 2024	- -

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.95
Cadd	Benign	0.027
Dann	Benign	0.46

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: rs61740901; hg19: chr16-75513469;