rs4805924

Variant names:

• chr19-33677367-C-T
• rs4805924
• NM_001127895.2:c.-87+9524C>T

Variant summary

Our verdict is Benign. The variant received -12 ACMG points: 0P and 12B. BP4_Strong BA1

The NM_001127895.2(CHST8):​c.-87+9524C>T variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0347 in 152,292 control chromosomes in the GnomAD database, including 149 homozygotes. In-silico tool predicts a benign outcome for this variant. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar.

• Frequency: Genomes: 𝑓 0.035 (149 hom., cov: 33)
• Consequence: CHST8 NM_001127895.2 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 0.0100
• Publications: 6 publications found

Genes affected

CHST8 (HGNC:15993): (carbohydrate sulfotransferase 8) The protein encoded by this gene belongs to the sulfotransferase 2 family. It is predominantly expressed in the pituitary gland, and is localized to the golgi membrane. This protein catalyzes the transfer of sulfate to position 4 of non-reducing N-acetylgalactosamine (GalNAc) residues in both N-glycans and O-glycans. It is responsible for sulfation of GalNAc on luteinizing hormone (LH), which is required for production of the sex hormones. Mice lacking this enzyme, exhibit increased levels of circulating LH, and precocious sexual maturation of both male and female mice. Alternatively spliced transcript variants have been found for this gene. [provided by RefSeq, Aug 2011]

CHST8 Gene-Disease associations (from GenCC):

• peeling skin syndrome type A

  Inheritance: AR Classification: SUPPORTIVE, LIMITED Submitted by: Orphanet, G2P

ACMG classification

Our verdict: Benign. The variant received -12 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.81).
• BA1: GnomAd4 highest subpopulation (SAS) allele frequency at 95% confidence interval = 0.0955 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
CHST8	NM_001127895.2	c.-87+9524C>T		intron_variant	Intron 2 of 4	ENST00000650847.1	NP_001121367.1
CHST8	NM_001127896.2	c.-86-11809C>T		intron_variant	Intron 1 of 3		NP_001121368.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
CHST8	ENST00000650847.1	c.-87+9524C>T		intron_variant	Intron 2 of 4		NM_001127895.2	ENSP00000499084.1

Frequencies

GnomAD3 genomes AF: 0.0346 AC: 5265 AN: 152174 Hom.: 144 Cov.: 33

Gnomad AFR AF: 0.0180

Gnomad AMI AF: 0.00329

Gnomad AMR AF: 0.0898

Gnomad ASJ AF: 0.0507

Gnomad EAS AF: 0.0653

Gnomad SAS AF: 0.103

Gnomad FIN AF: 0.0327

Gnomad MID AF: 0.0190

Gnomad NFE AF: 0.0250

Gnomad OTH AF: 0.0373

We have no GnomAD4 exomes data on this position. Probably position not covered by the project.

GnomAD4 genome AF: 0.0347 AC: 5284 AN: 152292 Hom.: 149 Cov.: 33 AF XY: 0.0381 AC XY: 2835 AN XY: 74466

African (AFR) AF: 0.0183 AC: 759 AN: 41550

American (AMR) AF: 0.0902 AC: 1380 AN: 15304

Ashkenazi Jewish (ASJ) AF: 0.0507 AC: 176 AN: 3472

East Asian (EAS) AF: 0.0653 AC: 338 AN: 5176

South Asian (SAS) AF: 0.103 AC: 497 AN: 4826

European-Finnish (FIN) AF: 0.0327 AC: 347 AN: 10614

Middle Eastern (MID) AF: 0.0204 AC: 6 AN: 294

European-Non Finnish (NFE) AF: 0.0250 AC: 1700 AN: 68032

Other (OTH) AF: 0.0369 AC: 78 AN: 2112

Alfa AF: 0.0305 Hom.: 322

Bravo AF: 0.0374

Asia WGS AF: 0.0980 AC: 340 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.81
CADD	Benign	5.3
DANN	Benign	0.73
PhyloP100		0.010
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: rs4805924; hg19: chr19-34168273;