rs16982149

Variant names:

• chr19-48576021-T-C
• rs16982149
• NM_177973.2:c.152T>C

Variant summary

Our verdict is Benign. The variant received -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. 16/22 in silico tools predict a benign outcome for this variant. Variant has been reported in ClinVar as Likely benign (★★).

• 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:4
• Conservation: PhyloP100: -0.342
• Publications: 18 publications found

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]

SULT2B1 Gene-Disease associations (from GenCC):

• ichthyosis, congenital, autosomal recessive 14

  Inheritance: AR Classification: STRONG, LIMITED Submitted by: G2P, Genomics England PanelApp, Labcorp Genetics (formerly Invitae), PanelApp Australia, Ambry Genetics
• lamellar ichthyosis

  Inheritance: AR Classification: SUPPORTIVE Submitted by: Orphanet

ENSG00000287603 (HGNC:):

ACMG classification

Our verdict: Benign. The variant received -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 Benign/Likely_benign. ClinVar VariationId 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 the male GnomAd4 subpopulation. Median coverage is 29. This position passed quality control check.
• BS2: High Homozygotes in GnomAd4 at 3 AR gene

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_177973.2. You can select a different transcript below to see updated ACMG assignments.

RefSeq Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	SULT2B1	NM_177973.2	MANE Select	c.152T>C	p.Leu51Ser	missense	Exon 2 of 7	NP_814444.1	O00204-1
	SULT2B1	NM_004605.2		c.107T>C	p.Leu36Ser	missense	Exon 1 of 6	NP_004596.2	O00204-2

Ensembl Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	SULT2B1	ENST00000201586.7	TSL:1 MANE Select	c.152T>C	p.Leu51Ser	missense	Exon 2 of 7	ENSP00000201586.2	O00204-1
	SULT2B1	ENST00000323090.4	TSL:1	c.107T>C	p.Leu36Ser	missense	Exon 1 of 6	ENSP00000312880.3	O00204-2
	ENSG00000287603	ENST00000666424.1		n.493+20725A>G		intron	N/A

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

GnomAD2 exomes AF: 0.00466 AC: 1159 AN: 248972 AF XY: 0.00478

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 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

African (AFR) AF: 0.00102 AC: 34 AN: 33478

American (AMR) AF: 0.000984 AC: 44 AN: 44724

Ashkenazi Jewish (ASJ) AF: 0.000497 AC: 13 AN: 26132

East Asian (EAS) AF: 0.0000252 AC: 1 AN: 39696

South Asian (SAS) AF: 0.000533 AC: 46 AN: 86258

European-Finnish (FIN) AF: 0.00425 AC: 227 AN: 53392

Middle Eastern (MID) AF: 0.00121 AC: 7 AN: 5768

European-Non Finnish (NFE) AF: 0.00891 AC: 9906 AN: 1111920

Other (OTH) AF: 0.00517 AC: 312 AN: 60390

GnomAD4 genome AF: 0.00429 AC: 652 AN: 152098 Hom.: 3 Cov.: 29 AF XY: 0.00370 AC XY: 275 AN XY: 74362

African (AFR) AF: 0.00118 AC: 49 AN: 41510

American (AMR) AF: 0.000985 AC: 15 AN: 15230

Ashkenazi Jewish (ASJ) AF: 0.00173 AC: 6 AN: 3470

East Asian (EAS) AF: 0.00 AC: 0 AN: 5168

South Asian (SAS) AF: 0.000831 AC: 4 AN: 4814

European-Finnish (FIN) AF: 0.00293 AC: 31 AN: 10596

Middle Eastern (MID) AF: 0.00340 AC: 1 AN: 294

European-Non Finnish (NFE) AF: 0.00787 AC: 535 AN: 68000

Other (OTH) AF: 0.00333 AC: 7 AN: 2104

Alfa AF: 0.00674 Hom.: 21

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

ClinVar submissions

Significance: Benign/Likely benign

Revision: criteria provided, multiple submitters, no conflicts

Pathogenic	VUS	Benign	Condition
-	-	3	not provided (3)
-	-	1	SULT2B1-related disorder (1)

Computational scores

Source: dbNSFP v4.9

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
M_CAP	Benign	0.0073	T
MetaRNN	Benign	0.0066	T
MetaSVM	Benign	-0.95	T
MutationAssessor	Benign	1.0	L
PhyloP100		-0.34
PrimateAI	Benign	0.30	T
PROVEAN	Benign	0.66	N
REVEL	Benign	0.030
Sift	Benign	0.91	T
Sift4G	Benign	0.49	T
Polyphen		0.0090	B
Vest4		0.24
MVP		0.093
MPC		0.39
ClinPred		0.0021	T
GERP RS		-1.5
PromoterAI		0.029	Neutral
Varity_R		0.062
gMVP		0.74
Mutation Taster		=98/2	polymorphism

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

Other links and lift over

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