chr19-48587291-C-T

Position:

• chr19-48587291-C-T

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.277C>T​(p.Arg93Cys) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.000722 in 1,614,032 control chromosomes in the GnomAD database, including 6 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Likely benign (★★).

• Frequency:
  • Genomes: 𝑓 0.00055 (0 hom., cov: 31)
  • Exomes 𝑓: 0.00074 (6 hom.)
• Consequence: SULT2B1 NM_177973.2 missense
• Clinical Significance: Likely benign criteria provided, multiple submitters, no conflicts B:2
• Conservation: PhyloP100: 1.19

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=0.016470373).
• BP6: Variant 19-48587291-C-T is Benign according to our data. Variant chr19-48587291-C-T is described in ClinVar as [Likely_benign]. Clinvar id is 778850.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars.
• BS1: Variant frequency is greater than expected in population sas. gnomad4 allele frequency = 0.000545 (83/152156) while in subpopulation SAS AF= 0.00353 (17/4820). AF 95% confidence interval is 0.00225. There are 0 homozygotes in gnomad4. There are 41 alleles in male gnomad4 subpopulation. Median coverage is 31. This position pass quality control queck.
• BS2: High Homozygotes in GnomAdExome4 at 6 AR gene

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
SULT2B1	NM_177973.2	c.277C>T	p.Arg93Cys	missense_variant	3/7	ENST00000201586.7	NP_814444.1
SULT2B1	NM_004605.2	c.232C>T	p.Arg78Cys	missense_variant	2/6		NP_004596.2

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
SULT2B1	ENST00000201586.7	c.277C>T	p.Arg93Cys	missense_variant	3/7	1	NM_177973.2	ENSP00000201586	P2
SULT2B1	ENST00000323090.4	c.232C>T	p.Arg78Cys	missense_variant	2/6	1		ENSP00000312880	A2
	ENST00000666424.1	n.493+9455G>A		intron_variant, non_coding_transcript_variant

Frequencies

GnomAD3 genomes AF: 0.000546 AC: 83 AN: 152038 Hom.: 0 Cov.: 31

Gnomad AFR AF: 0.0000966

Gnomad AMI AF: 0.00

Gnomad AMR AF: 0.000591

Gnomad ASJ AF: 0.000288

Gnomad EAS AF: 0.00

Gnomad SAS AF: 0.00352

Gnomad FIN AF: 0.00

Gnomad MID AF: 0.00

Gnomad NFE AF: 0.000735

Gnomad OTH AF: 0.000961

GnomAD3 exomes AF: 0.000948 AC: 238 AN: 251010 Hom.: 2 AF XY: 0.00122 AC XY: 165 AN XY: 135674

Gnomad AFR exome AF: 0.000123

Gnomad AMR exome AF: 0.000434

Gnomad ASJ exome AF: 0.000298

Gnomad EAS exome AF: 0.0000544

Gnomad SAS exome AF: 0.00327

Gnomad FIN exome AF: 0.00

Gnomad NFE exome AF: 0.000979

Gnomad OTH exome AF: 0.000979

GnomAD4 exome AF: 0.000740 AC: 1082 AN: 1461876 Hom.: 6 Cov.: 31 AF XY: 0.000869 AC XY: 632 AN XY: 727240

Gnomad4 AFR exome AF: 0.000209

Gnomad4 AMR exome AF: 0.000447

Gnomad4 ASJ exome AF: 0.000191

Gnomad4 EAS exome AF: 0.0000252

Gnomad4 SAS exome AF: 0.00339

Gnomad4 FIN exome AF: 0.000169

Gnomad4 NFE exome AF: 0.000584

Gnomad4 OTH exome AF: 0.00113

GnomAD4 genome AF: 0.000545 AC: 83 AN: 152156 Hom.: 0 Cov.: 31 AF XY: 0.000551 AC XY: 41 AN XY: 74388

Gnomad4 AFR AF: 0.0000963

Gnomad4 AMR AF: 0.000590

Gnomad4 ASJ AF: 0.000288

Gnomad4 EAS AF: 0.00

Gnomad4 SAS AF: 0.00353

Gnomad4 FIN AF: 0.00

Gnomad4 NFE AF: 0.000735

Gnomad4 OTH AF: 0.000951

Alfa AF: 0.000791 Hom.: 3

Bravo AF: 0.000461

TwinsUK AF: 0.00108 AC: 4

ALSPAC AF: 0.000519 AC: 2

ESP6500AA AF: 0.00 AC: 0

ESP6500EA AF: 0.000814 AC: 7

ExAC AF: 0.000988 AC: 120

Asia WGS AF: 0.00115 AC: 4 AN: 3478

EpiCase AF: 0.00120

EpiControl AF: 0.00160

ClinVar

Significance: Likely benign

Submissions summary: Benign:2

Revision: criteria provided, multiple submitters, no conflicts

Submissions by phenotype

not provided Benign:2

Likely benign, criteria provided, single submitter	clinical testing	CeGaT Center for Human Genetics Tuebingen	Mar 01, 2023	SULT2B1: BS2 -
Likely benign, criteria provided, single submitter	clinical testing	Labcorp Genetics (formerly Invitae), Labcorp	Dec 31, 2019	- -

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
AlphaMissense	Benign	0.089
BayesDel_addAF	Benign	-0.24	T
BayesDel_noAF	Benign	-0.12
CADD	Pathogenic	30
DANN	Pathogenic	1.0
DEOGEN2	Uncertain	0.58	D;.
Eigen	Uncertain	0.30
Eigen_PC	Benign	0.18
FATHMM_MKL	Benign	0.24	N
LIST_S2	Benign	0.82	T;T
M_CAP	Benign	0.050	D
MetaRNN	Benign	0.016	T;T
MetaSVM	Uncertain	0.33	D
MutationAssessor	Uncertain	2.6	M;.
MutationTaster	Benign	0.99	D;D
PrimateAI	Benign	0.27	T
PROVEAN	Pathogenic	-4.8	D;D
REVEL	Uncertain	0.47
Sift	Uncertain	0.0030	D;D
Sift4G	Uncertain	0.012	D;D
Polyphen		1.0	D;D
Vest4		0.34
MVP		0.63
MPC		1.1
ClinPred		0.070	T
GERP RS		5.0
Varity_R		0.55
gMVP		0.62

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: rs149116557; hg19: chr19-49090548; COSMIC: COSV52377998; COSMIC: COSV52377998;