19-48575967-G-A

Position:

• chr19-48575967-G-A

Variant summary

Our verdict is Benign. Variant got -14 ACMG points: 0P and 14B. BP4_Strong BP6_Moderate BA1

The NM_177973.2(SULT2B1):​c.98G>A​(p.Arg33Gln) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00363 in 1,613,454 control chromosomes in the GnomAD database, including 113 homozygotes. In-silico tool predicts a benign outcome for this variant. 14/20 in silico tools predict a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★).

• Frequency:
  • Genomes: 𝑓 0.0042 (23 hom., cov: 30)
  • Exomes 𝑓: 0.0036 (90 hom.)
• Consequence: SULT2B1 NM_177973.2 missense
• Clinical Significance: Benign criteria provided, single submitter B:2
• Conservation: PhyloP100: -0.299

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 -14 ACMG points.

• BP4: Computational evidence support a benign effect (MetaRNN=0.0017948747).
• BP6: Variant 19-48575967-G-A is Benign according to our data. Variant chr19-48575967-G-A is described in ClinVar as [Benign]. Clinvar id is 790920.Status of the report is criteria_provided_single_submitter, 1 stars.
• BA1: GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.0717 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
SULT2B1	NM_177973.2	c.98G>A	p.Arg33Gln	missense_variant	2/7	ENST00000201586.7	NP_814444.1
SULT2B1	NM_004605.2	c.53G>A	p.Arg18Gln	missense_variant	1/6		NP_004596.2

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
SULT2B1	ENST00000201586.7	c.98G>A	p.Arg33Gln	missense_variant	2/7	1	NM_177973.2	ENSP00000201586	P2
SULT2B1	ENST00000323090.4	c.53G>A	p.Arg18Gln	missense_variant	1/6	1		ENSP00000312880	A2
	ENST00000666424.1	n.493+20779C>T		intron_variant, non_coding_transcript_variant

Frequencies

GnomAD3 genomes AF: 0.00420 AC: 639 AN: 152042 Hom.: 23 Cov.: 30

Gnomad AFR AF: 0.000483

Gnomad AMI AF: 0.00

Gnomad AMR AF: 0.000986

Gnomad ASJ AF: 0.000577

Gnomad EAS AF: 0.0778

Gnomad SAS AF: 0.00579

Gnomad FIN AF: 0.00396

Gnomad MID AF: 0.00

Gnomad NFE AF: 0.00179

Gnomad OTH AF: 0.00288

GnomAD3 exomes AF: 0.00761 AC: 1893 AN: 248884 Hom.: 64 AF XY: 0.00724 AC XY: 975 AN XY: 134732

Gnomad AFR exome AF: 0.000123

Gnomad AMR exome AF: 0.000318

Gnomad ASJ exome AF: 0.00

Gnomad EAS exome AF: 0.0802

Gnomad SAS exome AF: 0.00291

Gnomad FIN exome AF: 0.00434

Gnomad NFE exome AF: 0.00167

Gnomad OTH exome AF: 0.00588

GnomAD4 exome AF: 0.00357 AC: 5223 AN: 1461296 Hom.: 90 Cov.: 30 AF XY: 0.00350 AC XY: 2545 AN XY: 726902

Gnomad4 AFR exome AF: 0.000239

Gnomad4 AMR exome AF: 0.000380

Gnomad4 ASJ exome AF: 0.000115

Gnomad4 EAS exome AF: 0.0564

Gnomad4 SAS exome AF: 0.00301

Gnomad4 FIN exome AF: 0.00521

Gnomad4 NFE exome AF: 0.00181

Gnomad4 OTH exome AF: 0.00668

GnomAD4 genome AF: 0.00420 AC: 639 AN: 152158 Hom.: 23 Cov.: 30 AF XY: 0.00471 AC XY: 350 AN XY: 74386

Gnomad4 AFR AF: 0.000482

Gnomad4 AMR AF: 0.000985

Gnomad4 ASJ AF: 0.000577

Gnomad4 EAS AF: 0.0780

Gnomad4 SAS AF: 0.00580

Gnomad4 FIN AF: 0.00396

Gnomad4 NFE AF: 0.00179

Gnomad4 OTH AF: 0.00285

Alfa AF: 0.00399 Hom.: 29

Bravo AF: 0.00434

TwinsUK AF: 0.00189 AC: 7

ALSPAC AF: 0.00156 AC: 6

ESP6500AA AF: 0.00 AC: 0

ESP6500EA AF: 0.00163 AC: 14

ExAC AF: 0.00749 AC: 910

Asia WGS AF: 0.0380 AC: 133 AN: 3478

ClinVar

Significance: Benign

Submissions summary: Benign:2

Revision: criteria provided, single submitter

Submissions by phenotype

SULT2B1-related disorder Benign:1

Benign, no assertion criteria provided

clinical testing

PreventionGenetics, part of Exact Sciences

Aug 22, 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). -

not provided Benign:1

Benign, criteria provided, single submitter

clinical testing

Labcorp Genetics (formerly Invitae), Labcorp

Sep 01, 2023

- -

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
AlphaMissense	Benign	0.083
BayesDel_addAF	Benign	-0.63	T
BayesDel_noAF	Benign	-0.61
CADD	Benign	13
DANN	Benign	0.96
DEOGEN2	Benign	0.053	T;.
Eigen	Benign	-0.87
Eigen_PC	Benign	-0.75
FATHMM_MKL	Benign	0.13	N
LIST_S2	Benign	0.65	T;T
MetaRNN	Benign	0.0018	T;T
MetaSVM	Benign	-0.90	T
MutationAssessor	Benign	1.8	L;.
MutationTaster	Benign	0.99	N;N
PrimateAI	Benign	0.24	T
PROVEAN	Benign	-0.16	N;N
REVEL	Benign	0.038
Sift	Benign	0.47	T;T
Sift4G	Benign	0.61	T;T
Polyphen		0.13	B;B
Vest4		0.11
MVP		0.082
MPC		0.32
ClinPred		0.0061	T
GERP RS		0.70
Varity_R		0.055
gMVP		0.54

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: rs117476816; hg19: chr19-49079224; COSMIC: COSV52374694;