19-48576021-T-C

Variant summary

Our verdict is Benign. Variant got -20 ACMG points: 0P and 20B. BP4_Strong BP6_Very_Strong BS1 BS2

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
• Clinical Significance: Benign/Likely benign criteria provided, multiple submitters, no conflicts B:3
• Conservation: PhyloP100: -0.342

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]

(HGNC:):

ACMG classification

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 GnomAd at 3 AR gene

Transcripts

RefSeq

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

Ensembl

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

Frequencies

GnomAD3 genomes AF: 0.00428 AC: 651 AN: 151980 Hom.: 3 Cov.: 29

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.: 6 AF XY: 0.00478 AC XY: 644 AN XY: 134776

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.: 55 Cov.: 32 AF XY: 0.00714 AC XY: 5195 AN XY: 727178

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.: 3 Cov.: 29 AF XY: 0.00370 AC XY: 275 AN XY: 74362

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.: 8

Bravo AF: 0.00411

TwinsUK AF: 0.00890 AC: 33

ALSPAC AF: 0.00675 AC: 26

ESP6500AA AF: 0.00113 AC: 5

ESP6500EA AF: 0.00628 AC: 54

ExAC AF: 0.00584 AC: 709

Asia WGS AF: 0.000577 AC: 2 AN: 3478

EpiCase AF: 0.00671

EpiControl AF: 0.00652

ClinVar

Significance: Benign/Likely benign

Submissions summary: Benign:3

Revision: criteria provided, multiple submitters, no conflicts

Submissions by phenotype

not provided Benign:2

Benign, criteria provided, single submitter	clinical testing	Invitae	Jan 02, 2024	- -
Likely benign, criteria provided, single submitter	clinical testing	CeGaT Center for Human Genetics Tuebingen	Jun 01, 2021	- -

SULT2B1-related disorder Benign:1

Benign, criteria provided, single submitter

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	T
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	N
LIST_S2	Benign	0.33	T;T
M_CAP	Benign	0.0073	T
MetaRNN	Benign	0.0066	T;T
MetaSVM	Benign	-0.95	T
MutationAssessor	Benign	1.0	L;.
MutationTaster	Benign	1.0	N;N
PrimateAI	Benign	0.30	T
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	T
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

Other links and lift over

dbSNP: rs16982149; hg19: chr19-49079278; COSMIC: COSV99079401;