chr19-48591599-C-T

Position:

• chr19-48591599-C-T

Variant summary

Our verdict is Benign. Variant got -20 ACMG points: 0P and 20B. BP4_Strong BP6_Very_Strong BA1

The NM_177973.2(SULT2B1):​c.424-10C>T variant causes a splice polypyrimidine tract, intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0445 in 1,608,084 control chromosomes in the GnomAD database, including 3,152 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★★).

• Frequency:
  • Genomes: 𝑓 0.038 (250 hom., cov: 31)
  • Exomes 𝑓: 0.045 (2902 hom.)
• Consequence: SULT2B1 NM_177973.2 splice_polypyrimidine_tract, intron
• Scores: Splicing: ADA: 0.0005432
• Clinical Significance: Benign criteria provided, multiple submitters, no conflicts B:3
• Conservation: PhyloP100: 0.704

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 (BayesDel_noAF=-0.76).
• BP6: Variant 19-48591599-C-T is Benign according to our data. Variant chr19-48591599-C-T is described in ClinVar as [Benign]. Clinvar id is 1601562.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars.
• BA1: GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.197 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
SULT2B1	NM_177973.2	c.424-10C>T		splice_polypyrimidine_tract_variant, intron_variant		ENST00000201586.7	NP_814444.1
SULT2B1	NM_004605.2	c.379-10C>T		splice_polypyrimidine_tract_variant, intron_variant			NP_004596.2

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
SULT2B1	ENST00000201586.7	c.424-10C>T		splice_polypyrimidine_tract_variant, intron_variant		1	NM_177973.2	ENSP00000201586	P2
SULT2B1	ENST00000323090.4	c.379-10C>T		splice_polypyrimidine_tract_variant, intron_variant		1		ENSP00000312880	A2
	ENST00000666424.1	n.493+5147G>A		intron_variant, non_coding_transcript_variant
SULT2B1	ENST00000594274.1	n.174-10C>T		splice_polypyrimidine_tract_variant, intron_variant, non_coding_transcript_variant		3

Frequencies

GnomAD3 genomes AF: 0.0380 AC: 5781 AN: 152028 Hom.: 249 Cov.: 31

Gnomad AFR AF: 0.00787

Gnomad AMI AF: 0.00

Gnomad AMR AF: 0.0635

Gnomad ASJ AF: 0.0444

Gnomad EAS AF: 0.207

Gnomad SAS AF: 0.0910

Gnomad FIN AF: 0.0371

Gnomad MID AF: 0.00633

Gnomad NFE AF: 0.0346

Gnomad OTH AF: 0.0384

GnomAD3 exomes AF: 0.0599 AC: 14776 AN: 246792 Hom.: 789 AF XY: 0.0577 AC XY: 7685 AN XY: 133290

Gnomad AFR exome AF: 0.00734

Gnomad AMR exome AF: 0.102

Gnomad ASJ exome AF: 0.0421

Gnomad EAS exome AF: 0.191

Gnomad SAS exome AF: 0.0867

Gnomad FIN exome AF: 0.0370

Gnomad NFE exome AF: 0.0324

Gnomad OTH exome AF: 0.0492

GnomAD4 exome AF: 0.0452 AC: 65826 AN: 1455938 Hom.: 2902 Cov.: 31 AF XY: 0.0456 AC XY: 33048 AN XY: 724068

Gnomad4 AFR exome AF: 0.00632

Gnomad4 AMR exome AF: 0.0986

Gnomad4 ASJ exome AF: 0.0416

Gnomad4 EAS exome AF: 0.250

Gnomad4 SAS exome AF: 0.0800

Gnomad4 FIN exome AF: 0.0369

Gnomad4 NFE exome AF: 0.0347

Gnomad4 OTH exome AF: 0.0490

GnomAD4 genome AF: 0.0380 AC: 5787 AN: 152146 Hom.: 250 Cov.: 31 AF XY: 0.0397 AC XY: 2949 AN XY: 74366

Gnomad4 AFR AF: 0.00785

Gnomad4 AMR AF: 0.0636

Gnomad4 ASJ AF: 0.0444

Gnomad4 EAS AF: 0.207

Gnomad4 SAS AF: 0.0911

Gnomad4 FIN AF: 0.0371

Gnomad4 NFE AF: 0.0346

Gnomad4 OTH AF: 0.0413

Alfa AF: 0.0361 Hom.: 253

Bravo AF: 0.0392

Asia WGS AF: 0.192 AC: 668 AN: 3478

ClinVar

Significance: 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	Labcorp Genetics (formerly Invitae), Labcorp	Jan 20, 2024	- -
Benign, criteria provided, single submitter	not provided	Breakthrough Genomics, Breakthrough Genomics	-	- -

SULT2B1-related disorder Benign:1

Benign, no assertion criteria provided

clinical testing

PreventionGenetics, part of Exact Sciences

Dec 05, 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
BayesDel_noAF	Benign	-0.76
CADD	Benign	6.9
DANN	Benign	0.64

Splicing

Name	Calibrated prediction	Score	Prediction
dbscSNV1_ADA	Benign	0.00054
dbscSNV1_RF	Benign	0.016
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: rs3745726; hg19: chr19-49094856; COSMIC: COSV52379497; COSMIC: COSV52379497;