dbSNP rs12460535: SULT2B1:c.646-1246A>G (chr19-48595493-A-G) – ACMG Classification: Benign (-12 pts)

Variant summary

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

The NM_177973.2(SULT2B1):c.646-1246A>G variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.578 in 151,806 control chromosomes in the GnomAD database, including 26,551 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 0.58 ( 26551 hom., cov: 29)

Consequence

SULT2B1
NM_177973.2 intron

Scores

Clinical Significance

Not reported in ClinVar

Conservation

PhyloP100: 0.776

Publications

13 publications found

Variant links:

Genes affected

SULT2B1 (HGNC:11459): (sulfotransferase family 2B member 1) Sulfotransferase enzymes catalyze the sulfate conjugation of many hormones, neurotransmitters, drugs, and xenobiotic compounds. These cytosolic enzymes are different in their tissue distributions and substrate specificities. The gene structure (number and length of exons) is similar among family members. This gene sulfates dehydroepiandrosterone but not 4-nitrophenol, a typical substrate for the phenol and estrogen sulfotransferase subfamilies. Two alternatively spliced variants that encode different isoforms have been described. [provided by RefSeq, Jul 2008]

SULT2B1 Gene-Disease associations (from GenCC):

ichthyosis, congenital, autosomal recessive 14
Inheritance: AR Classification: STRONG, LIMITED Submitted by: PanelApp Australia, Ambry Genetics, G2P, Labcorp Genetics (formerly Invitae), Genomics England PanelApp
lamellar ichthyosis
Inheritance: AR Classification: SUPPORTIVE Submitted by: Orphanet

SULT2B1 links:

ENSG00000287603 (HGNC:):

ENSG00000287603 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=-0.89).

BA1

GnomAd4 highest subpopulation (AMR) allele frequency at 95% confidence interval = 0.687 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
SULT2B1	NM_177973.2 link	c.646-1246A>G		intron_variant	Intron 5 of 6	ENST00000201586.7	NP_814444.1
SULT2B1	NM_004605.2 link	c.601-1246A>G		intron_variant	Intron 4 of 5		NP_004596.2

Ensembl

Gene	Transcript	HGVSc	Effect	Exon rank	TSL	MANE	Protein
SULT2B1	ENST00000201586.7 link	c.646-1246A>G	intron_variant	Intron 5 of 6	1	NM_177973.2	ENSP00000201586.2
SULT2B1	ENST00000323090.4 link	c.601-1246A>G	intron_variant	Intron 4 of 5	1		ENSP00000312880.3
SULT2B1	ENST00000594274.1 link	n.396-1246A>G	intron_variant	Intron 3 of 4	3
ENSG00000287603	ENST00000666424.1 link	n.493+1253T>C	intron_variant	Intron 1 of 2

Frequencies

GnomAD3 genomes

AF:

0.578

AC:

87714

AN:

151690

Hom.:

26551

Cov.:

show subpopulations

Gnomad AFR

AF:

0.408

Gnomad AMI

AF:

0.714

Gnomad AMR

AF:

0.698

Gnomad ASJ

AF:

0.594

Gnomad EAS

AF:

0.407

Gnomad SAS

AF:

0.601

Gnomad FIN

AF:

0.582

Gnomad MID

AF:

0.725

Gnomad NFE

AF:

0.661

Gnomad OTH

AF:

0.621

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

GnomAD4 genome

AF:

0.578

AC:

87745

AN:

151806

Hom.:

26551

Cov.:

AF XY:

0.577

AC XY:

42794

AN XY:

74134

show subpopulations

African (AFR)

AF:

0.408

AC:

16893

AN:

41404

American (AMR)

AF:

0.698

AC:

10627

AN:

15232

Ashkenazi Jewish (ASJ)

AF:

0.594

AC:

2061

AN:

3468

East Asian (EAS)

AF:

0.406

AC:

2085

AN:

5136

South Asian (SAS)

AF:

0.601

AC:

2890

AN:

4806

European-Finnish (FIN)

AF:

0.582

AC:

6131

AN:

10536

Middle Eastern (MID)

AF:

0.711

AC:

209

AN:

294

European-Non Finnish (NFE)

AF:

0.661

AC:

44903

AN:

67910

Other (OTH)

AF:

0.615

AC:

1298

AN:

2112

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.508

Heterozygous variant carriers

1762

3523

5285

7046

8808

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Genome Het

Genome Hom

Variant carriers

732

1464

2196

2928

3660

<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:

0.635

Hom.:

123363

Bravo

AF:

0.584

Asia WGS

AF:

0.463

AC:

1610

AN:

3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

BayesDel_noAF

Benign

-0.89

CADD

Benign

5.9

(source)

DANN

Benign

0.69

PhyloP100

0.78

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

You must be logged in to view publications. This limit was set because tens of millions (!) of queries from AI bots are generated daily.

Variant summary

Frequency

Consequence

Scores

Clinical Significance

Conservation

Publications

ACMG classification

Transcripts

RefSeq

Ensembl

Frequencies

Age Distribution

ClinVar

Computational scores

Splicing

Publications

Other links and lift over