Genetic Variant CHST8:c.131-30491A>T (chr19-33740922-A-T) – ACMG Classification: Benign (-12 pts)

Variant summary

Our verdict is Benign. The variant received -12 ACMG points: 0P and 12B. BP4_StrongBA1

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

Scores

Clinical Significance

Not reported in ClinVar

Conservation

PhyloP100: -0.424

Publications

3 publications found

Variant links:

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: G2P, Orphanet

CHST8 links:

Genome browser will be placed here

ACMG classification

Classification was made for transcript

Our verdict: Benign. The variant received -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.

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_001127895.2. You can select a different transcript below to see updated ACMG assignments.

RefSeq Transcripts

Gene	Transcript	Tags	HGVSc	Effect	Exon Rank	Protein	UniProt
CHST8	NM_001127895.2	MANE Select	c.131-30491A>T	intron	N/A	NP_001121367.1	Q9H2A9
CHST8	NM_001127896.2		c.131-30491A>T	intron	N/A	NP_001121368.1	Q9H2A9
CHST8	NM_022467.3		c.131-30491A>T	intron	N/A	NP_071912.2	Q9H2A9

Ensembl Transcripts

Gene	Transcript	Tags	HGVSc	Effect	Exon Rank	Protein	UniProt
CHST8	ENST00000650847.1	MANE Select	c.131-30491A>T	intron	N/A	ENSP00000499084.1	Q9H2A9
CHST8	ENST00000262622.4	TSL:1	c.131-30491A>T	intron	N/A	ENSP00000262622.3	Q9H2A9
CHST8	ENST00000438847.7	TSL:1	c.131-30491A>T	intron	N/A	ENSP00000393879.1	Q9H2A9

Frequencies

GnomAD3 genomes

AF:

0.0858

AC:

13046

AN:

152048

Hom.:

642

Cov.:

show subpopulations

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.:

AF XY:

0.0886

AC XY:

6587

AN XY:

74374

show subpopulations

African (AFR)

AF:

0.0386

AC:

1603

AN:

41524

American (AMR)

AF:

0.111

AC:

1701

AN:

15296

Ashkenazi Jewish (ASJ)

AF:

0.145

AC:

504

AN:

3470

East Asian (EAS)

AF:

0.0325

AC:

168

AN:

5176

South Asian (SAS)

AF:

0.0970

AC:

467

AN:

4816

European-Finnish (FIN)

AF:

0.140

AC:

1484

AN:

10582

Middle Eastern (MID)

AF:

0.0680

AC:

AN:

294

European-Non Finnish (NFE)

AF:

0.0995

AC:

6766

AN:

67986

Other (OTH)

AF:

0.0890

AC:

188

AN:

2112

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.502

Heterozygous variant carriers

600

1200

1801

2401

3001

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Genome Het

Genome Hom

Variant carriers

148

296

444

592

740

<30

30-35

35-40

40-45

45-50

50-55

55-60

60-65

65-70

70-75

75-80

>80

Age

Alfa

AF:

0.0908

Hom.:

Bravo

AF:

0.0829

Asia WGS

AF:

0.0800

AC:

278

AN:

3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name

Calibrated prediction

Score

Prediction

BayesDel_noAF

Benign

-0.84

CADD

Benign

1.2

(source)

DANN

Benign

0.68

PhyloP100

-0.42

Mutation Taster

=100/0

polymorphism (auto)

(source)

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

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Variant summary

Frequency

Consequence

Scores

Clinical Significance

Conservation

Publications

ACMG classification

Variant Effect in Transcripts

RefSeq Transcripts

Ensembl Transcripts

Frequencies

Age Distribution

ClinVar

Computational scores

Splicing

Publications

Other links and lift over