19-48576021-T-C

Position:

chr19-48576021-T-C

Variant summary

Our verdict is Benign. Variant got -20 ACMG points: 0P and 20B. BP4_StrongBP6_Very_StrongBS1BS2

The NM_177973.2(SULT2B1):c.152T>C(p.Leu51Ser) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00697 in 1,613,856 control chromosomes in the GnomAD database, including 58 homozygotes. In-silico tool predicts a benign outcome for this variant. 15/21 in silico tools predict a benign outcome for this variant. Variant has been reported in ClinVar as Likely benign (★★). Another nucleotide change resulting in same amino acid change has been previously reported as Likely benignin UniProt.

Frequency

Genomes: 𝑓 0.0043 ( 3 hom., cov: 29)

Exomes 𝑓: 0.0072 ( 55 hom. )

Consequence

SULT2B1
NM_177973.2 missense

Scores

Clinical Significance

Benign/Likely benign criteria provided, multiple submitters, no conflicts B:4

Conservation

PhyloP100: -0.342

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 links:

(HGNC:):

links:

Genome browser will be placed here

ACMG classification

Classification made for transcript

Verdict is Benign. Variant got -20 ACMG points.

BP4

Computational evidence support a benign effect (MetaRNN=0.0066310465).

BP6

Variant 19-48576021-T-C is Benign according to our data. Variant chr19-48576021-T-C is described in ClinVar as [Likely_benign]. Clinvar id is 726656.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars.

BS1

Variant frequency is greater than expected in population nfe. gnomad4 allele frequency = 0.00429 (652/152098) while in subpopulation NFE AF= 0.00787 (535/68000). AF 95% confidence interval is 0.00732. There are 3 homozygotes in gnomad4. There are 275 alleles in male gnomad4 subpopulation. Median coverage is 29. This position pass quality control queck.

BS2

High Homozygotes in GnomAd4 at 3 AR gene

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
SULT2B1	NM_177973.2 linkuse as main transcript	c.152T>C	p.Leu51Ser	missense_variant	2/7	ENST00000201586.7	NP_814444.1
SULT2B1	NM_004605.2 linkuse as main transcript	c.107T>C	p.Leu36Ser	missense_variant	1/6		NP_004596.2

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
SULT2B1	ENST00000201586.7 linkuse as main transcript	c.152T>C	p.Leu51Ser	missense_variant	2/7	1	NM_177973.2	ENSP00000201586	P2	O00204-1
SULT2B1	ENST00000323090.4 linkuse as main transcript	c.107T>C	p.Leu36Ser	missense_variant	1/6	1		ENSP00000312880	A2	O00204-2
	ENST00000666424.1 linkuse as main transcript	n.493+20725A>G		intron_variant, non_coding_transcript_variant

Frequencies

GnomAD3 genomes

AF:

0.00428

AC:

651

AN:

151980

Hom.:

Cov.:

show subpopulations

Gnomad AFR

AF:

0.00118

Gnomad AMI

AF:

0.00439

Gnomad AMR

AF:

0.000986

Gnomad ASJ

AF:

0.00173

Gnomad EAS

AF:

0.00

Gnomad SAS

AF:

0.000623

Gnomad FIN

AF:

0.00293

Gnomad MID

AF:

0.00316

Gnomad NFE

AF:

0.00787

Gnomad OTH

AF:

0.00336

GnomAD3 exomes

AF:

0.00466

AC:

1159

AN:

248972

Hom.:

AF XY:

0.00478

AC XY:

644

AN XY:

134776

show subpopulations

Gnomad AFR exome

AF:

0.00111

Gnomad AMR exome

AF:

0.00130

Gnomad ASJ exome

AF:

0.000696

Gnomad EAS exome

AF:

0.00

Gnomad SAS exome

AF:

0.000588

Gnomad FIN exome

AF:

0.00273

Gnomad NFE exome

AF:

0.00893

Gnomad OTH exome

AF:

0.00294

GnomAD4 exome

AF:

0.00724

AC:

10590

AN:

1461758

Hom.:

Cov.:

AF XY:

0.00714

AC XY:

5195

AN XY:

727178

show subpopulations

Gnomad4 AFR exome

AF:

0.00102

Gnomad4 AMR exome

AF:

0.000984

Gnomad4 ASJ exome

AF:

0.000497

Gnomad4 EAS exome

AF:

0.0000252

Gnomad4 SAS exome

AF:

0.000533

Gnomad4 FIN exome

AF:

0.00425

Gnomad4 NFE exome

AF:

0.00891

Gnomad4 OTH exome

AF:

0.00517

GnomAD4 genome

AF:

0.00429

AC:

652

AN:

152098

Hom.:

Cov.:

AF XY:

0.00370

AC XY:

275

AN XY:

74362

show subpopulations

Gnomad4 AFR

AF:

0.00118

Gnomad4 AMR

AF:

0.000985

Gnomad4 ASJ

AF:

0.00173

Gnomad4 EAS

AF:

0.00

Gnomad4 SAS

AF:

0.000831

Gnomad4 FIN

AF:

0.00293

Gnomad4 NFE

AF:

0.00787

Gnomad4 OTH

AF:

0.00333

Alfa

AF:

0.00662

Hom.:

Bravo

AF:

0.00411

TwinsUK

AF:

0.00890

AC:

ALSPAC

AF:

0.00675

AC:

ESP6500AA

AF:

0.00113

AC:

ESP6500EA

AF:

0.00628

AC:

ExAC

AF:

0.00584

AC:

709

Asia WGS

AF:

0.000577

AC:

AN:

3478

EpiCase

AF:

0.00671

EpiControl

AF:

0.00652

ClinVar

Significance: Benign/Likely benign

Submissions summary: Benign:4

Revision: criteria provided, multiple submitters, no conflicts

LINK: link

Submissions by phenotype

not provided

Benign:3

Likely benign, criteria provided, single submitter	clinical testing	CeGaT Center for Human Genetics Tuebingen	Jun 01, 2021	- -
Likely benign, criteria provided, single submitter	not provided	Breakthrough Genomics, Breakthrough Genomics	-	- -
Benign, criteria provided, single submitter	clinical testing	Labcorp Genetics (formerly Invitae), Labcorp	Jan 02, 2024	- -

SULT2B1-related disorder

Benign:1

Benign, no assertion criteria provided

clinical testing

PreventionGenetics, part of Exact Sciences

Sep 24, 2019

This variant is classified as benign based on ACMG/AMP sequence variant interpretation guidelines (Richards et al. 2015 PMID: 25741868, with internal and published modifications). -

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

AlphaMissense

Benign

0.13

BayesDel_addAF

Benign

-0.63

BayesDel_noAF

Benign

-0.67

CADD

Benign

5.3

DANN

Benign

0.35

DEOGEN2

Benign

0.067

T;.

Eigen

Benign

-1.2

Eigen_PC

Benign

-1.2

FATHMM_MKL

Benign

0.019

LIST_S2

Benign

0.33

T;T

M_CAP

Benign

0.0073

MetaRNN

Benign

0.0066

T;T

MetaSVM

Benign

-0.95

MutationAssessor

Benign

1.0

L;.

MutationTaster

Benign

1.0

N;N

PrimateAI

Benign

0.30

PROVEAN

Benign

0.66

N;N

REVEL

Benign

0.030

Sift

Benign

0.91

T;T

Sift4G

Benign

0.49

T;T

Polyphen

0.0090

B;B

Vest4

0.24

MVP

0.093

MPC

0.39

ClinPred

0.0021

GERP RS

-1.5

Varity_R

0.062

gMVP

0.74

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

Below is the list of publications found by LitVar. It may be empty.

Variant summary

Frequency

Consequence

Scores

Clinical Significance

Conservation

ACMG classification

Transcripts

RefSeq

Ensembl

Frequencies

ClinVar

Submissions by phenotype

Computational scores

Splicing

Publications

LitVar

Other links and lift over