Genetic Variant SULT1B1:p.Thr261Met (chr4-69727197-G-A) – ACMG Classification: Benign (-10 pts)

Variant summary

Our verdict is Benign. The variant received -10 ACMG points: 0P and 10B. BP4_StrongBP6_ModerateBS2

The NM_014465.4(SULT1B1):c.782C>T(p.Thr261Met) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00196 in 1,602,078 control chromosomes in the GnomAD database, including 10 homozygotes. In-silico tool predicts a benign outcome for this variant. 17/22 in silico tools predict a benign outcome for this variant. Variant has been reported in ClinVar as Likely benign (★).

Frequency

Genomes: 𝑓 0.0037 ( 8 hom., cov: 32)

Exomes 𝑓: 0.0018 ( 2 hom. )

Consequence

SULT1B1
NM_014465.4 missense

Scores

Clinical Significance

Likely benign criteria provided, single submitter B:1

Conservation

PhyloP100: -0.321

Variant links:

Genes affected

SULT1B1 (HGNC:17845): (sulfotransferase family 1B 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. However, the total genomic length of this gene is greater than that of other SULT1 genes. [provided by RefSeq, Jul 2008]

SULT1B1 links:

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ACMG classification

Classification was made for transcript

Our verdict: Benign. The variant received -10 ACMG points.

BP4

Computational evidence support a benign effect (MetaRNN=0.004876703).

BP6

Variant 4-69727197-G-A is Benign according to our data. Variant chr4-69727197-G-A is described in ClinVar as [Likely_benign]. Clinvar id is 2654791.Status of the report is criteria_provided_single_submitter, 1 stars.

BS2

High Homozygotes in GnomAd4 at 8 AR gene

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
SULT1B1	NM_014465.4 link	c.782C>T	p.Thr261Met	missense_variant	Exon 8 of 8	ENST00000310613.8	NP_055280.2	O43704

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
SULT1B1	ENST00000310613.8 link	c.782C>T	p.Thr261Met	missense_variant	Exon 8 of 8	1	NM_014465.4	ENSP00000308770.2		O43704

Frequencies

GnomAD3 genomes

AF:

0.00355

AC:

538

AN:

151738

Hom.:

Cov.:

show subpopulations

Gnomad AFR

AF:

0.00876

Gnomad AMI

AF:

0.00

Gnomad AMR

AF:

0.00112

Gnomad ASJ

AF:

0.00

Gnomad EAS

AF:

0.00

Gnomad SAS

AF:

0.000414

Gnomad FIN

AF:

0.000853

Gnomad MID

AF:

0.00

Gnomad NFE

AF:

0.00211

Gnomad OTH

AF:

0.00240

GnomAD2 exomes

AF:

0.00195

AC:

470

AN:

241204

AF XY:

0.00170

show subpopulations

Gnomad AFR exome

AF:

0.00855

Gnomad AMR exome

AF:

0.000783

Gnomad ASJ exome

AF:

0.00

Gnomad EAS exome

AF:

0.0000566

Gnomad FIN exome

AF:

0.00164

Gnomad NFE exome

AF:

0.00245

Gnomad OTH exome

AF:

0.000862

GnomAD4 exome

AF:

0.00178

AC:

2583

AN:

1450222

Hom.:

Cov.:

AF XY:

0.00168

AC XY:

1210

AN XY:

721472

show subpopulations

African (AFR)

AF:

0.00812

AC:

264

AN:

32530

American (AMR)

AF:

0.000736

AC:

AN:

42118

Ashkenazi Jewish (ASJ)

AF:

0.0000390

AC:

AN:

25654

East Asian (EAS)

AF:

0.00

AC:

AN:

39476

South Asian (SAS)

AF:

0.0000831

AC:

AN:

84232

European-Finnish (FIN)

AF:

0.00177

AC:

AN:

53112

Middle Eastern (MID)

AF:

0.00106

AC:

AN:

5686

European-Non Finnish (NFE)

AF:

0.00187

AC:

2076

AN:

1107574

Other (OTH)

AF:

0.00174

AC:

104

AN:

59840

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.454

Heterozygous variant carriers

116

232

347

463

579

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

GnomAD4 genome

AF:

0.00369

AC:

560

AN:

151856

Hom.:

Cov.:

AF XY:

0.00344

AC XY:

255

AN XY:

74222

show subpopulations

African (AFR)

AF:

0.00927

AC:

384

AN:

41432

American (AMR)

AF:

0.00112

AC:

AN:

15206

Ashkenazi Jewish (ASJ)

AF:

0.00

AC:

AN:

3460

East Asian (EAS)

AF:

0.00

AC:

AN:

5156

South Asian (SAS)

AF:

0.000415

AC:

AN:

4822

European-Finnish (FIN)

AF:

0.000853

AC:

AN:

10556

Middle Eastern (MID)

AF:

0.00

AC:

AN:

294

European-Non Finnish (NFE)

AF:

0.00211

AC:

143

AN:

67910

Other (OTH)

AF:

0.00237

AC:

AN:

2108

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.508

Heterozygous variant carriers

123

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Alfa

AF:

0.00277

Hom.:

Bravo

AF:

0.00366

TwinsUK

AF:

0.000809

AC:

ALSPAC

AF:

0.00285

AC:

ESP6500AA

AF:

0.00862

AC:

ESP6500EA

AF:

0.00186

AC:

ExAC

AF:

0.00243

AC:

295

Asia WGS

AF:

0.00318

AC:

AN:

3478

ClinVar

Significance: Likely benign

Submissions summary: Benign:1

Revision: criteria provided, single submitter

LINK: link

Submissions by phenotype

not provided

Benign:1

Jan 01, 2023

CeGaT Center for Human Genetics Tuebingen

Significance:Likely benign

Review Status:criteria provided, single submitter

Collection Method:clinical testing

SULT1B1: BP4, BS2 -

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

AlphaMissense

Benign

0.075

BayesDel_addAF

Benign

-0.48

BayesDel_noAF

Benign

-0.45

CADD

Benign

0.010

(source)

DANN

Benign

0.18

DEOGEN2

Benign

0.14

Eigen

Benign

-1.4

Eigen_PC

Benign

-1.4

FATHMM_MKL

Benign

0.0030

LIST_S2

Benign

0.41

M_CAP

Benign

0.021

MetaRNN

Benign

0.0049

MetaSVM

Benign

-0.95

MutationAssessor

Benign

0.95

PhyloP100

-0.32

PrimateAI

Benign

0.27

PROVEAN

Benign

0.34

REVEL

Benign

0.057

Sift

Benign

0.57

Sift4G

Benign

0.32

Polyphen

0.017

Vest4

0.12

MVP

0.42

MPC

0.016

ClinPred

0.0011

GERP RS

-0.067

Varity_R

0.017

gMVP

0.37

Mutation Taster

=97/3

polymorphism

(source)

Splicing

Name

Calibrated prediction

Score

Prediction

SpliceAI score (max)

0.12

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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4-69727197-G-A

Variant summary

Frequency

Consequence

Scores

Clinical Significance

Conservation

ACMG classification

Transcripts

RefSeq

Ensembl

Frequencies

Age Distribution

Age Distribution

ClinVar

Submissions by phenotype

Computational scores

Splicing

Publications

Other links and lift over