19-48591686-G-A

Variant summary

Our verdict is Benign. Variant got -15 ACMG points: 0P and 15B. BP4_Moderate BP6_Very_Strong BP7 BS1

The NM_177973.2(SULT2B1):c.501G>A(p.Lys167=) variant causes a synonymous change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00264 in 1,613,044 control chromosomes in the GnomAD database, including 7 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Likely benign (★★).

• Frequency:
  • Genomes: 𝑓 0.0019 (0 hom., cov: 31)
  • Exomes 𝑓: 0.0027 (7 hom.)
• Consequence: SULT2B1 NM_177973.2 synonymous
• Clinical Significance: Benign/Likely benign criteria provided, multiple submitters, no conflicts B:2
• Conservation: PhyloP100: 0.384

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 -15 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.44).
• BP6: Variant 19-48591686-G-A is Benign according to our data. Variant chr19-48591686-G-A is described in ClinVar as [Likely_benign]. Clinvar id is 720878.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars.
• BP7: Synonymous conserved (PhyloP=0.384 with no splicing effect.
• BS1: Variant frequency is greater than expected in population nfe. gnomad4 allele frequency = 0.00189 (287/152202) while in subpopulation NFE AF= 0.00287 (195/68004). AF 95% confidence interval is 0.00254. There are 0 homozygotes in gnomad4. There are 136 alleles in male gnomad4 subpopulation. Median coverage is 31. This position pass quality control queck.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
SULT2B1	NM_177973.2	c.501G>A	p.Lys167=	synonymous_variant	4/7	ENST00000201586.7
SULT2B1	NM_004605.2	c.456G>A	p.Lys152=	synonymous_variant	3/6

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
SULT2B1	ENST00000201586.7	c.501G>A	p.Lys167=	synonymous_variant	4/7	1	NM_177973.2	P2
SULT2B1	ENST00000323090.4	c.456G>A	p.Lys152=	synonymous_variant	3/6	1		A2
	ENST00000666424.1	n.493+5060C>T		intron_variant, non_coding_transcript_variant
SULT2B1	ENST00000594274.1	n.251G>A		non_coding_transcript_exon_variant	2/5	3

Frequencies

GnomAD3 genomes AF: 0.00189 AC: 287 AN: 152084 Hom.: 0 Cov.: 31

Gnomad AFR AF: 0.000579

Gnomad AMI AF: 0.00

Gnomad AMR AF: 0.00269

Gnomad ASJ AF: 0.00461

Gnomad EAS AF: 0.00

Gnomad SAS AF: 0.000416

Gnomad FIN AF: 0.00

Gnomad MID AF: 0.00

Gnomad NFE AF: 0.00287

Gnomad OTH AF: 0.00430

GnomAD3 exomes AF: 0.00191 AC: 476 AN: 249484 Hom.: 0 AF XY: 0.00201 AC XY: 271 AN XY: 134892

Gnomad AFR exome AF: 0.000624

Gnomad AMR exome AF: 0.00169

Gnomad ASJ exome AF: 0.00471

Gnomad EAS exome AF: 0.00

Gnomad SAS exome AF: 0.000659

Gnomad FIN exome AF: 0.0000930

Gnomad NFE exome AF: 0.00283

Gnomad OTH exome AF: 0.00329

GnomAD4 exome AF: 0.00272 AC: 3977 AN: 1460842 Hom.: 7 Cov.: 31 AF XY: 0.00270 AC XY: 1962 AN XY: 726656

Gnomad4 AFR exome AF: 0.000568

Gnomad4 AMR exome AF: 0.00175

Gnomad4 ASJ exome AF: 0.00476

Gnomad4 EAS exome AF: 0.00

Gnomad4 SAS exome AF: 0.000918

Gnomad4 FIN exome AF: 0.000131

Gnomad4 NFE exome AF: 0.00314

Gnomad4 OTH exome AF: 0.00277

GnomAD4 genome AF: 0.00189 AC: 287 AN: 152202 Hom.: 0 Cov.: 31 AF XY: 0.00183 AC XY: 136 AN XY: 74412

Gnomad4 AFR AF: 0.000578

Gnomad4 AMR AF: 0.00269

Gnomad4 ASJ AF: 0.00461

Gnomad4 EAS AF: 0.00

Gnomad4 SAS AF: 0.000416

Gnomad4 FIN AF: 0.00

Gnomad4 NFE AF: 0.00287

Gnomad4 OTH AF: 0.00426

Alfa AF: 0.00272 Hom.: 1

Bravo AF: 0.00221

Asia WGS AF: 0.000577 AC: 2 AN: 3478

EpiCase AF: 0.00311

EpiControl AF: 0.00416

ClinVar

Significance: Benign/Likely benign

Submissions summary: Benign:2

Revision: criteria provided, multiple submitters, no conflicts

Submissions by phenotype

SULT2B1-related disorder Benign:1

Likely benign, criteria provided, single submitter

clinical testing

PreventionGenetics, part of Exact Sciences

Dec 11, 2019

This variant is classified as likely 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

Invitae

Dec 07, 2023

- -

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.44
Cadd	Benign	8.4
Dann	Benign	0.45

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: rs149312079; hg19: chr19-49094943;