rs17325700

Positions:

• chr19-33740922-A-T

Variant summary

Our verdict is Benign. Variant got -12 ACMG points: 0P and 12B. BP4_Strong BA1

The NM_001127895.2(CHST8):​c.131-30491A>T variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0859 in 152,166 control chromosomes in the GnomAD database, including 648 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 0.086 (648 hom., cov: 32)
• Consequence: CHST8 NM_001127895.2 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.424

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]

ACMG classification

Verdict is Benign. Variant got -12 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.84).
• BA1: GnomAd4 highest subpopulation (AMR) allele frequency at 95% confidence interval = 0.107 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
CHST8	NM_001127895.2	c.131-30491A>T		intron_variant		ENST00000650847.1	NP_001121367.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
CHST8	ENST00000650847.1	c.131-30491A>T		intron_variant			NM_001127895.2	ENSP00000499084	P1

Frequencies

GnomAD3 genomes AF: 0.0858 AC: 13046 AN: 152048 Hom.: 642 Cov.: 32

Gnomad AFR AF: 0.0382

Gnomad AMI AF: 0.193

Gnomad AMR AF: 0.111

Gnomad ASJ AF: 0.145

Gnomad EAS AF: 0.0322

Gnomad SAS AF: 0.0954

Gnomad FIN AF: 0.140

Gnomad MID AF: 0.0823

Gnomad NFE AF: 0.0996

Gnomad OTH AF: 0.0866

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

GnomAD4 genome AF: 0.0859 AC: 13077 AN: 152166 Hom.: 648 Cov.: 32 AF XY: 0.0886 AC XY: 6587 AN XY: 74374

Gnomad4 AFR AF: 0.0386

Gnomad4 AMR AF: 0.111

Gnomad4 ASJ AF: 0.145

Gnomad4 EAS AF: 0.0325

Gnomad4 SAS AF: 0.0970

Gnomad4 FIN AF: 0.140

Gnomad4 NFE AF: 0.0995

Gnomad4 OTH AF: 0.0890

Alfa AF: 0.0908 Hom.: 79

Bravo AF: 0.0829

Asia WGS AF: 0.0800 AC: 278 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.84
CADD	Benign	1.2
DANN	Benign	0.68

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: rs17325700; hg19: chr19-34231827;